首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1322928457453273330, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.11.023, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793340323079, onlineDateStr=2026-10-30, pubDate=1762704000000, pubDateStr=2025-11-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793340323079, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793340323079, creator=13701087609, updateTime=1793340323079, updator=13701087609, issue=Issue{id=1322926985957221241, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='11', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1762704000000', pubDateStr='2025-11-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339972247, creator='13701087609', updateTime=1793340743335, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322930220201804556, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322930220201804557, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=107, endPage=116, ext={EN=ArticleExt(id=1322928457725903091, articleId=1322928457453273330, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research on Biological Mechanism of PD of Kidney Essence Deficiency Syndrome Based on Glucose Metabolism and Intervention Effect of Dihuang Yinzi（地黄饮子）, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To explore the biological mechanism of Parkinson's disease（PD）of kidney essence deficiency syndrome from the perspective of glucose metabolism and the mechanism of intervention of Dihuang Yinzi（地黄饮子）in PD of kidney essence deficiency syndrome.

Methods

Fifty-five SPF grade male 12-week-old SAM-P8 mice were divided into model group，positive drug group，Dihuang Yinzi low，middle and high dose groups，with 11 mice in each group，and 11 SAM-R1 mice were as the normal group. The PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine（MPTP）（30 mg/kg，once a day）into SAM-P8 mice for 7 days，and the intervention lasted for 4 weeks. The general status indicators of mice was observed，and the fasting blood glucose levels and behavioral indicators in mice were measured. HE staining was used to observe the structural changes of mouse kidney and testis. Western blot（WB），immunohistochemistry and polymerase chain reaction（PCR）were used to detect the protein contents of glucose transporter 1（GLUT1），glucose transporter 3（GLUT3），glucose transporter 4（GLUT4），and glycogen synthase kinase 3β（GSK-3β）in the substantia nigra and striatum of mouse brain tissue.

Results

In the open field experiment，compared with the normal group，the model group showed a decrease in total exercise distance（P<0.05）and an increase in latency（P<0.05）. Compared with that of the model group，the latency of mice in the Dihuang Yinzi low and high dose groups decreased（P<0.05）. The total distance of mice in the Dihuang Yinzi middle dose group increased（P<0.05）. In the pole climbing experiment，compared with the normal group，the model group showed an increase in pole climbing time（P<0.05）. Compared with the model group，the Dihuang Yinzi low and high groups showed a decrease in time（P<0.05）. Compared with those before administration，the Dihuang Yinzi low，middle and high dose groups showed a decrease in time（P<0.05）. In the gait experiment，compared with the normal group，the model group showed significant differences in right anterior contact area，left anterior propulsion time，right posterior propulsion index，left posterior support phase and right anterior support phase（P<0.01）. Compared with that in the model group，there was a significant difference in the right posterior propulsion index（P<0.01）in the Dihuang Yinzi low dose group. There were significant differences in the contact area of the right forelimb，right posterior propulsion index，left posterior support phase，and right anterior support phase in the Dihuang Yinzi middle dose group（P<0.01）. There were significant differences in the contact area of the right forelimb，left posterior support phase and right anterior support phase in the Dihuang Yinzi high dose group（P<0.01）. HE renal staining test results showed compared with the blank group，the model group showed pathological changes such as glomerular epithelial cell proliferation，increased lipid droplets，renal tubular dilation，increased cell debris，increased red blood cells，increased lymphocytes，increased fibroblasts and increased fibroblasts. Compared with the model group，the Dihuang Yinzi high dose group showed a decrease in lipid droplets，red blood cells and fibroblasts. The HE testicular staining results showed that compared with the blank group，the model group showed pathological changes such as vacuolization of the spermatogenic epithelium and decreased sperm count. Compared with the model group，the Dihuang Yinzi high dose group showed reduced vacuolization of the spermatogenic epithelium. WB detection results showed compared with the normal group，the model group showed a significant decrease in GLUT1 protein expression in the substantia nigra（P<0.01），and a decrease in protein expressions of GLUT3 and GLUT4（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed a significant increase in protein expressions of GLUT1 and GLUT4 protein expression（P<0.01，P<0.05）and GSK-3βprotein expression decreased（P<0.05）. Compared with the normal group，the protein expressions of GLUT1 and GLUT3 in the striatum of the model group decreased significantly（P<0.01），and the expression of GLUT4 protein decreased（P<0.05）. The protein expression of GSK-3βincreased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed an increase in protein expression of GLUT1，GLUT3 and GLUT4（P<0.05，P<0.01），and GSK-3βprotein expression decreased（P<0.05）. Real time fluorescence quantitative PCR detection results showed compared with the normal group，the mRNA expressions of GLUT1，GLUT3 and GLUT4 in the substantia nigra of the model group mice were significantly reduced（P<0.01），and GSK-3βexpression increased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed increased expressions of GLUT1，GLUT3 and GLUT4（P<0.05），and GSK-3βexpression decreased（P<0.05）. Compared with the normal group，the mRNA expressions of GLUT1 and GLUT3 in the striatum of the model group were significantly lower（P<0.01），the expression of GLUT4 was lower（P<0.05）and the expression of GSK-3βincreased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed increased expressions of GLUT1，GLUT3 and GLUT4（P<0.05），and GSK-3βexpression decreased（P<0.05）. Immunohistochemical test results showed compared with the normal group，the expressions of GLUT1 and GLUT4 in the substantia nigra of the model group decreased（P<0.05），and GSK-3βexpression increased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group significantly increased the expression of GLUT1（P<0.01）. Compared with the normal group，the expressions of GLUT1 and GLUT4 in the striatum of the model group decreased significantly（P<0.01，P<0.05），respectively. Compared with the model group，the Dihuang Yinzi high dose group significantly increased the expressions of GLUT1，GLUT3 and GLUT4（P<0.01，P<0.05），and the expression of GSK-3βdecreased（P<0.05）.

Conclusion

1. Dihuang Yinzi can improve the motor speed，grip ability，limb coordination and exploration ability of PD mice with kidney essence deficiency syndrome.2. Dihuang Yinzi can reduce fasting blood glucose in mice with PD kidney essence deficiency syndrome，improve energy metabolism by correcting glucose metabolism.3. Dihuang Yinzi can increase the protein expressions of GLUT1 and GLUT4 in the substantia nigra of PD mice with kidney essence deficiency syndrome，and reduce the protein expression of GSK-3βin the substantia nigra of the brain，increase the expressions of GLUT1，GLUT3 and GLUT4 in the brain striatum，and reduce the expression of GSK-3β in the brain striatum. The protein expression in the Dihuang Yinzi middle and high dose groups was higher than that in the Dihuang Yinzi low dose group.4. Dihuang Yinzi has abnormal intake of GLUT1，GLUT3，GLUT4 and GSK-3βproteins. Dihuang Yinzi can treat PD of kidney essence deficiency syndrome by regulating the expressions of GLUT1，GLUT3，GLUT4 and GSK-3β proteins in the substantia nigra and striatum of PD mice.

, authors=Yafei ZHAO, Cheng HAN, Yuting ZHAO, Shaochuang LI, Qianyu QING, Qiong ZHAO, authorsList=Yafei ZHAO, Cheng HAN, Yuting ZHAO, Shaochuang LI, Qianyu QING, Qiong ZHAO, authorCompany=null, correspAuthors=Qiong ZHAO, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322928465980293410, articleId=1322928457453273330, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=基于糖代谢的帕金森病肾精虚证生物学机制及地黄饮子的干预作用研究, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=
目的

从糖代谢层面探讨帕金森病（Parkinson's disease，PD）肾精虚证的生物学机制和地黄饮子干预帕金森病肾精虚证的作用机制。

方法

采用SPF级雄性12周龄的SAM-P8小鼠55只，分为模型组、阳性药组、地黄饮子低剂量组、地黄饮子中剂量组、地黄饮子高剂量组每组11只和SAM-R1小鼠11只作为正常组，SAM-P8小鼠腹腔注射1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-Methyl-4-phenyl-1，2，3，6-tetrahydropyridine，MPTP）（30 mg/kg，1次/d）7 d建立PD模型，地黄饮子干预4周。观察小鼠一般状态指标，测定小鼠空腹血糖值、行为学指标。采用HE染色观察小鼠肾脏及睾丸组织结构变化，采用蛋白免疫印迹法（Western blot，WB）、免疫组化法、聚合酶链式反应（Polymerase chain reaction，PCR）检测小鼠脑组织中黑质、纹状体葡萄糖转运蛋白1（Glucose transporter 1，GLUT 1）、葡萄糖转运蛋白3（Glucose transporter 3，GLUT 3）、葡萄糖转运蛋白4（Glucose transporter 4，GLUT 4）、糖原合成激酶3β（Glycogen synthase kinase-3β，GSK-3β）蛋白含量。

结果

在旷场实验中，与正常组相比，模型组小鼠运动总路程减少（P<0.05），潜伏期增加（P<0.05）；与模型组相比，地黄饮子低、高剂量组小鼠潜伏期降低（P<0.05）；地黄饮子中剂量组小鼠总路程增加（P<0.05）。在爬杆实验中，与正常组比较，模型组爬杆时间增加（P<0.05）；与模型组相比，地黄饮子低、高剂量组时间降低（P<0.05）；与给药前相比，地黄饮子低、中、高剂量组时间降低（P<0.05）。在步态实验中，与正常组相比，模型组小鼠右前接触面积、左前推进时间、右后推进指数、左后支撑时相、右前支撑时相差异有统计学意义（P<0.01）；与模型组比较，地黄饮子低剂量组小鼠右后推进指数差异有统计学意义（P<0.01），地黄饮子中剂量组小鼠右前肢接触面积、右后推进指数、左后支撑时相、右前支撑时相差异有统计学意义（P<0.01），地黄饮子高剂量组小鼠右前肢接触面积、左后支撑时相、右前支撑时相差异有统计学意义（P<0.01）。HE肾脏染色检测结果：与正常组相比，模型组出现肾小球囊上皮细胞增生、脂滴增加、肾小管扩张、细胞碎片增加、红细胞增加、淋巴细胞增加、成纤维细胞增加、纤维细胞增加等病理改变。与模型组相比，地黄饮子高剂量组出现脂滴降低、红细胞降低、纤维细胞降低。HE睾丸染色结果显示：与正常组相比，模型组见生精上皮空泡化、精子数量减少等病变现象。与模型组相比，地黄饮子高剂量组出现生精上皮空泡化减轻。Westernblot检测结果：与正常组相比，模型组小鼠黑质GLUT1蛋白表达显著降低（P<0.01），GLUT3和GLUT4蛋白表达降低（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1蛋白表达显著增加（P<0.01），GLUT4蛋白表达增加（P<0.05），GSK-3β蛋白表达降低（P<0.05）。与正常组相比，模型组小鼠纹状体GLUT1和GLUT3蛋白表达显著降低（P<0.01），GLUT4蛋白表达降低（P<0.05），GSK-3β蛋白表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1蛋白表达增高（P<0.05），GLUT3蛋白表达显著增高（P<0.01），GLUT4蛋白表达升高（P<0.05），GSK-3β蛋白表达降低（P<0.05）。实时荧光定量PCR检测结果：与正常组相比，模型组小鼠黑质GLUT1、GLUT3、GLUT4 mRNA表达显著降低（P<0.01），GSK-3β表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1、GLUT3、GLUT4表达增高（P<0.05），GSK-3β表达降低（P<0.05）。与正常组相比，模型组小鼠纹状体GLUT1和GLUT3 mRNA表达显著降低（P<0.01），GLUT4表达降低（P<0.05），GSK-3β表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1、GLUT3、GLUT4表达增高（P<0.05），GSK-3β表达降低（P<0.05）。免疫组化检测结果：与正常组相比，模型组小鼠黑质GLUT1、GLUT4的表达降低（P<0.05），GSK-3β表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1表达显著升高（P<0.01）。与正常组相比，模型组小鼠纹状体GLUT1表达显著降低（P<0.01），GLUT4表达降低（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1、GLUT3表达显著增高（P<0.01），GLUT4表达升高（P<0.05），GSK-3β表达降低（P<0.05）。

结论

①地黄饮子能够提高PD肾精虚证小鼠运动速度、改善抓握能力、增强四肢协调性、增强对新环境的探索能力。②地黄饮子能够降低PD肾精虚证小鼠空腹血糖，通过纠正糖代谢，改善机体能量代谢。③地黄饮子能够提高PD肾精虚证小鼠脑黑质GLUT1、GLUT4蛋白的表达，降低脑黑质GSK-3β蛋白的表达，提高脑纹状体GLUT1、GLUT3、GLUT4的表达，降低脑纹状体GSK-3β蛋白的表达，地黄饮子中、高剂量组效果高于地黄饮子低剂量组。④帕金森病肾精虚证存在GLUT1、GLUT3、GLUT4、GSK-3β蛋白的摄入异常，地黄饮子可以通过调节帕金森病小鼠黑质、纹状体中GLUT1、GLUT3、GLUT4、GSK-3β蛋白的表达，治疗帕金森病肾精虚证。

, authors=赵雅飞, 韩诚, 赵玉婷, 李少创, 青千裕, 赵琼, authorsList=赵雅飞, 韩诚, 赵玉婷, 李少创, 青千裕, 赵琼, authorCompany=null, correspAuthors=赵琼, authorNote=

赵雅飞（1994-），女，河南平顶山人，硕士，研究方向：藏象理论。

, correspAuthorsNote=
赵琼（1979-），女，山西晋中人，副教授，硕士研究生导师，博士，研究方向：藏象理论。E-mail：。
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=n2yl9AG1bbYc0/HeZoeL4A==, magXml=xQXpZ+HApBBbJDxJes1+ZA==, pdfUrl=null, pdf=328qMgKZt8uYzLEbQ+ZZfQ==, pdfFileSize=8585939, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=OWXXnXbv84QLbevCRDms0A==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=izWB2YOQSliZ7opbkmWflw==, mapNumber=null, fund=null)}, authors=[Author(id=1322928466424889639, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928466517164329, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466424889639, language=EN, stringName=Yafei ZHAO, firstName=Yafei, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928466622021930, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466424889639, language=CN, stringName=赵雅飞, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio={"content":"

赵雅飞（1994-），女，河南平顶山人，硕士，研究方向：藏象理论。

"}, bioImg=null, bioContent=

赵雅飞（1994-），女，河南平顶山人，硕士，研究方向：藏象理论。

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928466726879532, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928466823348526, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466726879532, language=EN, stringName=Cheng HAN, firstName=Cheng, middleName=null, lastName=HAN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928466894651695, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466726879532, language=CN, stringName=韩诚, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928466970149169, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928467058229555, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466970149169, language=EN, stringName=Yuting ZHAO, firstName=Yuting, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928467150504244, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466970149169, language=CN, stringName=赵玉婷, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928467221807414, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928467293110584, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467221807414, language=EN, stringName=Shaochuang LI, firstName=Shaochuang, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928467368608057, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467221807414, language=CN, stringName=李少创, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928467439911227, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928467540574525, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467439911227, language=EN, stringName=Qianyu QING, firstName=Qianyu, middleName=null, lastName=QING, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928467628654910, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467439911227, language=CN, stringName=青千裕, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928469297987904, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=413568433@qq.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322928469402845506, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928469297987904, language=EN, stringName=Qiong ZHAO, firstName=Qiong, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928469490925891, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928469297987904, language=CN, stringName=赵琼, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])])], keywords=[Keyword(id=1322928469599977796, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, orderNo=1, keyword=Parkinson's disease), Keyword(id=1322928469679669573, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, orderNo=2, keyword=kidney essence deficiency syndrome), Keyword(id=1322928469780332870, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, orderNo=3, keyword=sugar metabolism), Keyword(id=1322928469847441735, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, orderNo=4, keyword=Dihuang Yinzi（地黄饮子）), Keyword(id=1322928469918744904, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, orderNo=5, keyword=glucose transporter protein), Keyword(id=1322928469998436681, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, orderNo=1, keyword=帕金森病), Keyword(id=1322928470069739850, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, orderNo=2, keyword=肾精虚证), Keyword(id=1322928470153625931, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, orderNo=3, keyword=糖代谢), Keyword(id=1322928470224929100, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, orderNo=4, keyword=地黄饮子), Keyword(id=1322928470296232269, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, orderNo=5, keyword=葡萄糖转运蛋白)], refs=[Reference(id=1322928476432499067, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2010, volume=37, issue=8, pageStart=1464, pageEnd=1465, url=null, language=null, rfNumber=［1］, rfOrder=0, authorNames=闫川慧, 张俊龙, 郭蕾, journalName=辽宁中医杂志, refType=null, unstructuredReference=闫川慧，张俊龙，郭蕾，等. 颤振中医治疗方案的文献研究［J］. 辽宁中医杂志，2010，37（8）：1464-1465., articleTitle=颤振中医治疗方案的文献研究, refAbstract=null), Reference(id=1322928476516385148, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2019, volume=19, issue=99, pageStart=117, pageEnd=118, url=null, language=null, rfNumber=［2］, rfOrder=1, authorNames=陈桑桑, 李清华, journalName=世界最新医学信息文摘, refType=null, unstructuredReference=陈桑桑，李清华. 帕金森病与糖尿病相关机制研究进展［J］. 世界最新医学信息文摘，2019，19（99）：117-118., articleTitle=帕金森病与糖尿病相关机制研究进展, refAbstract=null), Reference(id=1322928476591882621, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2022, volume=32, issue=1, pageStart=48, pageEnd=56, url=null, language=null, rfNumber=［3］, rfOrder=2, authorNames=王孟迪, 魏山山, 姜宁, journalName=中国比较医学杂志, refType=null, unstructuredReference=王孟迪，魏山山，姜宁，等. 金钗石斛对MPTP诱导PD小鼠的神经保护作用及机制研究［J］. 中国比较医学杂志，2022，32（1）：48-56., articleTitle=金钗石斛对MPTP诱导PD小鼠的神经保护作用及机制研究, refAbstract=null), Reference(id=1322928477833396606, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2021, volume=53, issue=17, pageStart=38, pageEnd=41, url=null, language=null, rfNumber=［4］, rfOrder=3, authorNames=朱斌, 王策, 徐青青, journalName=新中医, refType=null, unstructuredReference=朱斌，王策，徐青青. 地黄饮子联合认知康复治疗帕金森病轻度认知障碍临床研究［J］. 新中医，2021，53（17）：38-41., articleTitle=地黄饮子联合认知康复治疗帕金森病轻度认知障碍临床研究, refAbstract=null), Reference(id=1322928477908894079, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2018, volume=33, issue=3, pageStart=1063, pageEnd=1066, url=null, language=null, rfNumber=［5］, rfOrder=4, authorNames=成金枝, 张俊龙, 郭蕾, journalName=中华中医药杂志, refType=null, unstructuredReference=成金枝，张俊龙，郭蕾，等. 阿尔茨海默病肾虚证病证结合动物模型的制备及验证［J］. 中华中医药杂志，2018，33（3）：1063-1066., articleTitle=阿尔茨海默病肾虚证病证结合动物模型的制备及验证, refAbstract=null), Reference(id=1322928477980197248, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2015, volume=42, issue=3, pageStart=277, pageEnd=285, url=null, language=null, rfNumber=［6］, rfOrder=5, authorNames=胡雅岑, 徐倩, 郭纪峰, journalName=生物化学与生物物理进展, refType=null, unstructuredReference=胡雅岑，徐倩，郭纪峰，等. MPTP诱导的帕金森病小鼠模型黑质脑组织DNA甲基化研究［J］. 生物化学与生物物理进展，2015，42（3）：277-285., articleTitle=MPTP诱导的帕金森病小鼠模型黑质脑组织DNA甲基化研究, refAbstract=null), Reference(id=1322928478059889025, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2022, volume=31, issue=20, pageStart=12, pageEnd=17, url=null, language=null, rfNumber=［7］, rfOrder=6, authorNames=李玉明, 廖程娟, 朱沅如, journalName=中国民族民间医药, refType=null, unstructuredReference=李玉明，廖程娟，朱沅如，等. 白簕中性多糖对2型糖尿病小鼠糖脂代谢的作用［J］. 中国民族民间医药，2022，31（20）：12-17., articleTitle=白簕中性多糖对2型糖尿病小鼠糖脂代谢的作用, refAbstract=null), Reference(id=1322928478173135234, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2021, volume=57, issue=2, pageStart=178, pageEnd=181, url=null, language=null, rfNumber=［8］, rfOrder=7, authorNames=于锦锦, 薛雁, 刘翠, journalName=青岛大学学报（医学版）, refType=null, unstructuredReference=于锦锦，薛雁，刘翠，等. 苍白球大麻素对大鼠运动行为的调控及受体机制［J］. 青岛大学学报（医学版），2021，57（2）：178-181., articleTitle=苍白球大麻素对大鼠运动行为的调控及受体机制, refAbstract=null), Reference(id=1322928478248632707, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2020, volume=35, issue=7, pageStart=3623, pageEnd=3626, url=null, language=null, rfNumber=［9］, rfOrder=8, authorNames=李艳荣, 樊慧杰, 柴智, journalName=中华中医药杂志, refType=null, unstructuredReference=李艳荣，樊慧杰，柴智，等. 五子衍宗丸对帕金森病小鼠的神经保护及抗炎作用［J］. 中华中医药杂志，2020，35（7）：3623-3626., articleTitle=五子衍宗丸对帕金森病小鼠的神经保护及抗炎作用, refAbstract=null), Reference(id=1322928478328324484, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2021, volume=26, issue=null, pageStart=5702, pageEnd=5714, url=null, language=null, rfNumber=［10］, rfOrder=9, authorNames=RYU W I, BORMANN M K, SHEN M Q, journalName=Mol Psychiatry, refType=null, unstructuredReference=RYU W I，BORMANN M K，SHEN M Q，et al. Brain cells derived from Alzheimer’s disease patients have multiple specific innate abnormalities in energy metabolism［J］. Mol Psychiatry，2021，26：5702-5714., articleTitle=Brain cells derived from Alzheimer’s disease patients have multiple specific innate abnormalities in energy metabolism, refAbstract=null), Reference(id=1322928478408016261, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2019, volume=32, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=［11］, rfOrder=10, authorNames=VIHAR P, THOMAS R, SHAHRIAR S, journalName=Modern Pathology, refType=null, unstructuredReference=VIHAR P，THOMAS R，SHAHRIAR S，et al. Energy metabolism deficits in Alzheimer disease［J］. Modern Pathology，2019，32., articleTitle=Energy metabolism deficits in Alzheimer disease, refAbstract=null), Reference(id=1322928478487708038, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2018, volume=20, issue=12, pageStart=2145, pageEnd=2149, url=null, language=null, rfNumber=［12］, rfOrder=11, authorNames=文雯, 高丽娟, 魏江平, journalName=世界科学技术-中医药现代化, refType=null, unstructuredReference=文雯，高丽娟，魏江平，等. 能量代谢与阿尔茨海默病研究进展［J］. 世界科学技术-中医药现代化，2018，20（12）：2145-2149., articleTitle=能量代谢与阿尔茨海默病研究进展, refAbstract=null), Reference(id=1322928478563205511, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=1984, volume=81, issue=22, pageStart=7233, pageEnd=7237, url=null, language=null, rfNumber=［13］, rfOrder=12, authorNames=DICK A P, HARIK SI, KLIP A, journalName=Proc Natl Acad Sci USA, refType=null, unstructuredReference=DICK A P，HARIK SI，KLIP A，et al. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity［J］. Proc Natl Acad Sci USA，1984，81（22）：7233-7237., articleTitle=Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity, refAbstract=null), Reference(id=1322928478647091592, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2019, volume=91, issue=null, pageStart=90, pageEnd=93, url=null, language=null, rfNumber=［14］, rfOrder=13, authorNames=KOCH H, WEBER Y G, journalName=Epilepsy Behav, refType=null, unstructuredReference=KOCH H，WEBER Y G. The glucose transporter type1（Glut1）syndromes［J］. Epilepsy Behav，2019，91：90-93., articleTitle=The glucose transporter type1（Glut1）syndromes, refAbstract=null), Reference(id=1322928478730977673, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2019, volume=71, issue=2, pageStart=350, pageEnd=360, url=null, language=null, rfNumber=［15］, rfOrder=14, authorNames=魏兰兰, 任煦, 赵妍妍, journalName=生理学报, refType=null, unstructuredReference=魏兰兰，任煦，赵妍妍，等. 易化型葡萄糖转运体的表达、分布及相关疾病的研究进展［J］. 生理学报，2019，71（2）：350-360., articleTitle=易化型葡萄糖转运体的表达、分布及相关疾病的研究进展, refAbstract=null), Reference(id=1322928478919721354, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2020, volume=36, issue=1, pageStart=12, pageEnd=16, url=null, language=null, rfNumber=［16］, rfOrder=15, authorNames=衣雪洁, 孙玉霞, 姚婷婷, journalName=中国应用生理学杂志, refType=null, unstructuredReference=衣雪洁，孙玉霞，姚婷婷，等. 急、慢性运动对2型糖尿病大鼠脂肪PI3K/AKT/GLUT4通路的影响［J］. 中国应用生理学杂志，2020，36（1）：12-16., articleTitle=急、慢性运动对2型糖尿病大鼠脂肪PI3K/AKT/GLUT4通路的影响, refAbstract=null), Reference(id=1322928479007801739, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2020, volume=11, issue=3, pageStart=76, pageEnd=98, url=null, language=null, rfNumber=［17］, rfOrder=16, authorNames=WANG T N, WANGJ, HU X G, journalName=World JBiol Chem, refType=null, unstructuredReference=WANG T N，WANGJ，HU X G，et al. Current understanding of glucose transporter 4 expression and functional mechanisms［J］. World JBiol Chem，2020，11（3）：76-98., articleTitle=Current understanding of glucose transporter 4 expression and functional mechanisms, refAbstract=null), Reference(id=1322928479095882124, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2011, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=［18］, rfOrder=17, authorNames=刘佩, journalName=null, refType=null, unstructuredReference=刘佩. 益智健脑颗粒对AD模型大鼠海马胰岛素受体和葡萄糖转运蛋白4mRNA表达的影响［D］. 长沙：中南大学，2011., articleTitle=益智健脑颗粒对AD模型大鼠海马胰岛素受体和葡萄糖转运蛋白4mRNA表达的影响, refAbstract=null), Reference(id=1322928479167185293, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2009, volume=19, issue=19, pageStart=5582, pageEnd=5585, url=null, language=null, rfNumber=［19］, rfOrder=18, authorNames=MISHRA N, BASU A, JAYAPRAKASH V, journalName=Bioorg Med Chem Lett, refType=null, unstructuredReference=MISHRA N，BASU A，JAYAPRAKASH V，et al. Structure based virtual screening of GSK-3β：importance of protein flexibility and induced fit［J］. Bioorg Med Chem Lett，2009，19（19）：5582-5585., articleTitle=Structure based virtual screening of GSK-3β：importance of protein flexibility and induced fit, refAbstract=null), Reference(id=1322928479255265678, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=7, pageStart=10796, pageEnd=10813, url=null, language=null, rfNumber=［20］, rfOrder=19, authorNames=VALLÉE A, VALLÉE J N, LECARPENTIER Y, journalName=Aging（Albany NY）, refType=null, unstructuredReference=VALLÉE A，VALLÉE J N，LECARPENTIER Y. Potential role of cannabidiol in Parkinson’s disease by targeting the WNT/β-catenin pathway，oxidative stress and inflammation［J］. Aging（Albany NY），2021，13（7）：10796-10813., articleTitle=Potential role of cannabidiol in Parkinson’s disease by targeting the WNT/β-catenin pathway，oxidative stress and inflammation, refAbstract=null), Reference(id=1322928479330763151, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2023, volume=210, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=［21］, rfOrder=20, authorNames=KHAN SS, JANRAOS, SRIVASTAVA S, journalName=Biochem Pharmacol, refType=null, unstructuredReference=KHAN SS，JANRAOS，SRIVASTAVA S，et al. GSK-3β：an exuberating neuroinflammatory mediator in Parkinson’s disease［J］. Biochem Pharmacol，2023，210：115496., articleTitle=GSK-3β：an exuberating neuroinflammatory mediator in Parkinson’s disease, refAbstract=null), Reference(id=1322928479532089744, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2021, volume=22, issue=16, pageStart=9098, pageEnd=null, url=null, language=null, rfNumber=［22］, rfOrder=21, authorNames=DEMURO S, DIMARTINOR M C, ORTEGA JA, journalName=Int JMol Sci, refType=null, unstructuredReference=DEMURO S，DIMARTINOR M C，ORTEGA JA，et al. GSK-3β，FYN，and DYRK1A：master regulators in neurodegenerative pathways［J］. Int JMol Sci，2021，22（16）：9098., articleTitle=GSK-3β，FYN，and DYRK1A：master regulators in neurodegenerative pathways, refAbstract=null), Reference(id=1322928479624364433, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2018, volume=33, issue=20, pageStart=3104, pageEnd=3106, url=null, language=null, rfNumber=［23］, rfOrder=22, authorNames=杨远滨, 沈沁暄, journalName=光明中医, refType=null, unstructuredReference=杨远滨，沈沁暄. 帕金森病中医研究现状［J］. 光明中医，2018，33（20）：3104-3106., articleTitle=帕金森病中医研究现状, refAbstract=null), Reference(id=1322928479708250514, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2015, volume=284, issue=null, pageStart=138, pageEnd=152, url=null, language=null, rfNumber=［24］, rfOrder=23, authorNames=TONG JJ, CHEN G H, WANG F, journalName=Behav Brain Res, refType=null, unstructuredReference=TONG JJ，CHEN G H，WANG F，et al. Chronic acarbose treatment alleviates age-related behavioral and biochemical changes in SAMP8 mice［J］. Behav Brain Res，2015，284：138-152., articleTitle=Chronic acarbose treatment alleviates age-related behavioral and biochemical changes in SAMP8 mice, refAbstract=null), Reference(id=1322928479787942291, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2017, volume=25, issue=1, pageStart=1, pageEnd=7, url=null, language=null, rfNumber=［25］, rfOrder=24, authorNames=孙筱璇, 薛莉, 周畅, journalName=中国临床神经科学, refType=null, unstructuredReference=孙筱璇，薛莉，周畅，等. 晚期糖基化终末产物受体对帕金森病模型小鼠脑内酪氨酸羟化酶表达的影响［J］. 中国临床神经科学，2017，25（1）：1-7., articleTitle=晚期糖基化终末产物受体对帕金森病模型小鼠脑内酪氨酸羟化酶表达的影响, refAbstract=null), Reference(id=1322928479867634068, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2021, volume=31, issue=5, pageStart=41, pageEnd=46, url=null, language=null, rfNumber=［26］, rfOrder=25, authorNames=周丽丽, 莫超然, 刘心朗, journalName=中国比较医学杂志, refType=null, unstructuredReference=周丽丽，莫超然，刘心朗，等. 蒙药香青兰总黄酮对帕金森病模型小鼠的神经保护作用［J］. 中国比较医学杂志，2021，31（5）：41-46., articleTitle=蒙药香青兰总黄酮对帕金森病模型小鼠的神经保护作用, refAbstract=null), Reference(id=1322928479968297365, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, doi=null, pmid=null, pmcid=null, year=2009, volume=29, issue=6, pageStart=548, pageEnd=550, url=null, language=null, rfNumber=［27］, rfOrder=26, authorNames=沈自尹, 黄建华, 林伟, journalName=中国中西医结合杂志, refType=null, unstructuredReference=沈自尹，黄建华，林伟，等. 从整体论到系统生物学进行肾虚和衰老的研究［J］. 中国中西医结合杂志，2009，29（6）：548-550., articleTitle=从整体论到系统生物学进行肾虚和衰老的研究, refAbstract=null)], funds=[Fund(id=1322928476319252858, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, awardId=8187152326, language=CN, fundingSource=国家自然科学基金项目(8187152326), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])], figs=[ArticleFig(id=1322928470505947470, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=CCR1MObmcTDshi424yu5ww==, figureFileBig=OWXXnXbv84QLbevCRDms0A==, tableContent=null), ArticleFig(id=1322928470724051279, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图1, caption=地黄饮子对PD肾精虚证小鼠空腹血糖的影响（n＝11，）, figureFileSmall=CCR1MObmcTDshi424yu5ww==, figureFileBig=OWXXnXbv84QLbevCRDms0A==, tableContent=null), ArticleFig(id=1322928470979903824, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=vDX3sW99ii3j7FEGLFjHZQ==, figureFileBig=q/hcl87fH6RUF1u02bzvVA==, tableContent=null), ArticleFig(id=1322928471055401297, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图2, caption=肾脏组织病理HE染色（×200）, figureFileSmall=vDX3sW99ii3j7FEGLFjHZQ==, figureFileBig=q/hcl87fH6RUF1u02bzvVA==, tableContent=null), ArticleFig(id=1322928471139287378, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=8EpRGqA7z0hJ9v3OZwLmBQ==, figureFileBig=GOc3Su6goAjLnDonqV6ABw==, tableContent=null), ArticleFig(id=1322928471214784851, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图3, caption=睾丸组织病理HE染色（×200）, figureFileSmall=8EpRGqA7z0hJ9v3OZwLmBQ==, figureFileBig=GOc3Su6goAjLnDonqV6ABw==, tableContent=null), ArticleFig(id=1322928471286088020, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=KYkcNg0Jv5aeX3jzNkC+2Q==, figureFileBig=zCPBozfSOBH22stmNbm97A==, tableContent=null), ArticleFig(id=1322928471369974101, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图4, caption=地黄饮子对PD肾精虚证小鼠脑黑质中GLUT1和GLUT3、GLUT4和GSK-3β蛋白表达影响（n＝6，）, figureFileSmall=KYkcNg0Jv5aeX3jzNkC+2Q==, figureFileBig=zCPBozfSOBH22stmNbm97A==, tableContent=null), ArticleFig(id=1322928471445471574, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=mhk5n5NdbVb8miLKhLBnww==, figureFileBig=zi6q9Z1UlHZlzCZxFYCKrQ==, tableContent=null), ArticleFig(id=1322928471558717783, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图5, caption=地黄饮子对PD肾精虚证小鼠脑纹状体中GLUT1和GLUT3、GLUT4和GSK-3β蛋白表达影响（n＝6，）, figureFileSmall=mhk5n5NdbVb8miLKhLBnww==, figureFileBig=zi6q9Z1UlHZlzCZxFYCKrQ==, tableContent=null), ArticleFig(id=1322928471625826648, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=axJaYoN60AjRbD2l8rqf1A==, figureFileBig=Nk8HbLftda+qW0pgV/j67w==, tableContent=null), ArticleFig(id=1322928471705518425, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图6, caption=各组小鼠黑质内GLUT1免疫组化比较（×400）, figureFileSmall=axJaYoN60AjRbD2l8rqf1A==, figureFileBig=Nk8HbLftda+qW0pgV/j67w==, tableContent=null), ArticleFig(id=1322928471781015898, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=DnuVZ44qa7WGXt6jhVjHpA==, figureFileBig=Up0Upu67BpMMXs/92S690A==, tableContent=null), ArticleFig(id=1322928471864901979, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图7, caption=各组小鼠黑质内GLUT3免疫组化比较（×400）, figureFileSmall=DnuVZ44qa7WGXt6jhVjHpA==, figureFileBig=Up0Upu67BpMMXs/92S690A==, tableContent=null), ArticleFig(id=1322928471940399452, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=P66V9YRcsgsrx98L8A2u0w==, figureFileBig=QBumOErKQK4owSh1HaE4NA==, tableContent=null), ArticleFig(id=1322928472020091229, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图8, caption=各组小鼠黑质内GLUT4免疫组化比较（×400）, figureFileSmall=P66V9YRcsgsrx98L8A2u0w==, figureFileBig=QBumOErKQK4owSh1HaE4NA==, tableContent=null), ArticleFig(id=1322928472095588702, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=GyzYVZVzLzsIw1uDyopfTg==, figureFileBig=/7vRnUnGE1qXIGRJnOJDXQ==, tableContent=null), ArticleFig(id=1322928473781698911, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图9, caption=各组小鼠黑质内GSK3β免疫组化比较（×400）, figureFileSmall=GyzYVZVzLzsIw1uDyopfTg==, figureFileBig=/7vRnUnGE1qXIGRJnOJDXQ==, tableContent=null), ArticleFig(id=1322928473865584992, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=562e2qrh2aC1clWldZt2tw==, figureFileBig=MtK2/Jbru/eK+/dX2CxCww==, tableContent=null), ArticleFig(id=1322928474075300193, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图10, caption=各组小鼠纹状体内GLUT1免疫组化比较（×400）, figureFileSmall=562e2qrh2aC1clWldZt2tw==, figureFileBig=MtK2/Jbru/eK+/dX2CxCww==, tableContent=null), ArticleFig(id=1322928474184352098, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=AKGOs1hkBZN5xXBVkk0Dhg==, figureFileBig=IWyPLFuAM9Q0yfA6vL256w==, tableContent=null), ArticleFig(id=1322928474268238179, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图11, caption=各组小鼠纹状体内GLUT3免疫组化比较（×400）, figureFileSmall=AKGOs1hkBZN5xXBVkk0Dhg==, figureFileBig=IWyPLFuAM9Q0yfA6vL256w==, tableContent=null), ArticleFig(id=1322928474360512868, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=72WkZX2hITdqFqNneom01A==, figureFileBig=WprdmAFSVg3ddEXe9JpiVw==, tableContent=null), ArticleFig(id=1322928474440204645, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图12, caption=各组小鼠纹状体内GLUT4免疫组化比较（×400）, figureFileSmall=72WkZX2hITdqFqNneom01A==, figureFileBig=WprdmAFSVg3ddEXe9JpiVw==, tableContent=null), ArticleFig(id=1322928474515702118, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=0UTRNGLaaZsCUiR5WFC4Tw==, figureFileBig=0LOMGIYWpzIZq+onWbpyag==, tableContent=null), ArticleFig(id=1322928474654114151, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=图13, caption=各组小鼠纹状体内GSK3β免疫组化比较（×400）, figureFileSmall=0UTRNGLaaZsCUiR5WFC4Tw==, figureFileBig=0LOMGIYWpzIZq+onWbpyag==, tableContent=null), ArticleFig(id=1322928474784137576, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别蒸馏水MPTP盐酸美金刚地黄饮子水煎剂
正常组0.03 g/（kg·d），腹腔注射
1.55 g/（kg·d），灌胃
模型组1.55 g/（kg·d），灌胃0.03g/（kg·d），腹腔注射
阳性药组0.03 g/（kg·d），腹腔注射0.1 g/（kg·d），灌胃
地黄饮子低剂量组0.03 g/（kg·d），腹腔注射0.76 g/（kg·d），灌胃
地黄饮子中剂量组0.03 g/（kg·d），腹腔注射1.55 g/（kg·d），灌胃
地黄饮子高剂量组0.03 g/（kg·d），腹腔注射3.10 g/（kg·d），灌胃
), ArticleFig(id=1322928474851246441, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表1, caption=

各组给药剂量及处理方法

, figureFileSmall=null, figureFileBig=null, tableContent=
组别蒸馏水MPTP盐酸美金刚地黄饮子水煎剂
正常组0.03 g/（kg·d），腹腔注射
1.55 g/（kg·d），灌胃
模型组1.55 g/（kg·d），灌胃0.03g/（kg·d），腹腔注射
阳性药组0.03 g/（kg·d），腹腔注射0.1 g/（kg·d），灌胃
地黄饮子低剂量组0.03 g/（kg·d），腹腔注射0.76 g/（kg·d），灌胃
地黄饮子中剂量组0.03 g/（kg·d），腹腔注射1.55 g/（kg·d），灌胃
地黄饮子高剂量组0.03 g/（kg·d），腹腔注射3.10 g/（kg·d），灌胃
), ArticleFig(id=1322928474930938218, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
引物和探针引物序列（5′-3′）
GLUT1FACAGCCGATGTGACCCGAGAC
GLUT1RCAGCACCACAGCGATGAGGATG
GLUT3FCGCTGCCTTCCTCATCTTCTTCC
GLUT3RCGAAAGTCCTGCCTTTGGLCTCC
GLUT4FGGCTGTGAGTGAGTGCTIT
GLUT4RGGTITCTGCTCCCTATCGT
GSK-3βFGGCTGTGTGTTGGCTGAATTGTTG
GSK-3βRTTTGCTCCCTTGTTGGTGTTCCTAG
β-actinFCTCCATCATGAAGTGCGACGT
β-actinRGTGATCTCCTTCTGCATCCTGTC
), ArticleFig(id=1322928475014824299, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表2, caption=

引物与探针序列

, figureFileSmall=null, figureFileBig=null, tableContent=
引物和探针引物序列（5′-3′）
GLUT1FACAGCCGATGTGACCCGAGAC
GLUT1RCAGCACCACAGCGATGAGGATG
GLUT3FCGCTGCCTTCCTCATCTTCTTCC
GLUT3RCGAAAGTCCTGCCTTTGGLCTCC
GLUT4FGGCTGTGAGTGAGTGCTIT
GLUT4RGGTITCTGCTCCCTATCGT
GSK-3βFGGCTGTGTGTTGGCTGAATTGTTG
GSK-3βRTTTGCTCCCTTGTTGGTGTTCCTAG
β-actinFCTCCATCATGAAGTGCGACGT
β-actinRGTGATCTCCTTCTGCATCCTGTC
), ArticleFig(id=1322928475086127468, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别n总路程/（cm）总时间/（s）平均速度/（cm/s）静止时间/（s）跨格次数/（次）潜伏期/（s）
正常组115 599.91±635.93299.83±0.7618.63±1.6228.18±7.939.55±2.2327.78±16.47
模型组113 948.75±664.28*299.03±1.5613.39±2.3236.18±4.676.54±1.9444.52±20.81*
阳性药组113 910.52±635.93298.90±2.3913.92±2.9136.09±12.137.90±1.4434.90±14.72
地黄饮子低剂量组113 917.09±457.18298.02±3.1013.18±1.4136.65±10.367.81±2.0434.40±14.13
地黄饮子中剂量组114 570.95±643.01#299.95±0.3313.68±2.1331.77±10.017.34±1.6331.12±22.26#
地黄饮子高剂量组113 902.14±782.67299.85±0.6714.03±2.6137.02±10.387.86±2.0129.29±32.48#
), ArticleFig(id=1322928475165819245, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表3, caption=

地黄饮子对PD肾精虚证小鼠旷场实验的影响（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别n总路程/（cm）总时间/（s）平均速度/（cm/s）静止时间/（s）跨格次数/（次）潜伏期/（s）
正常组115 599.91±635.93299.83±0.7618.63±1.6228.18±7.939.55±2.2327.78±16.47
模型组113 948.75±664.28*299.03±1.5613.39±2.3236.18±4.676.54±1.9444.52±20.81*
阳性药组113 910.52±635.93298.90±2.3913.92±2.9136.09±12.137.90±1.4434.90±14.72
地黄饮子低剂量组113 917.09±457.18298.02±3.1013.18±1.4136.65±10.367.81±2.0434.40±14.13
地黄饮子中剂量组114 570.95±643.01#299.95±0.3313.68±2.1331.77±10.017.34±1.6331.12±22.26#
地黄饮子高剂量组113 902.14±782.67299.85±0.6714.03±2.6137.02±10.387.86±2.0129.29±32.48#
), ArticleFig(id=1322928475245511022, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别n给药前爬杆时间/（s）给药后爬杆时间/（s）
正常组118.14±2.896.57±1.80
模型组1112.74±4.13*11.58±2.94*
阳性药组1111.18±2.699.86±1.92
地黄饮子低剂量组1112.63±2.777.95±1.71#△
地黄饮子中剂量组1112.01±3.908.99±1.75△
地黄饮子高剂量组1112.24±2.708.33±1.42#△
), ArticleFig(id=1322928475333591407, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表4, caption=

地黄饮子对PD肾精虚证小鼠爬杆时间的影响（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别n给药前爬杆时间/（s）给药后爬杆时间/（s）
正常组118.14±2.896.57±1.80
模型组1112.74±4.13*11.58±2.94*
阳性药组1111.18±2.699.86±1.92
地黄饮子低剂量组1112.63±2.777.95±1.71#△
地黄饮子中剂量组1112.01±3.908.99±1.75△
地黄饮子高剂量组1112.24±2.708.33±1.42#△
), ArticleFig(id=1322928475404894576, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
步态指标n左前肢接触面积/（m2）右前肢接触面积/（m2）左后肢接触面积/（m2）右后肢接触面积/（m2）左前推进时间/（s）左后推进指数/（s）
正常组110.13±0.030.16±0.060.17±0.060.19±0.560.23±0.120.25±0.06
模型组110.13±0.050.24±0.06**0.16±0.060.23±0.55*0.36±0.18**0.27±0.06
阳性药组110.10±0.020.25±0.040.14±0.010.21±0.030.24±0.080.25±0.03
地黄饮子低剂量组110.11±0.040.21±0.030.14±0.100.17±0.060.24±0.050.25±0.01
地黄饮子低剂量组110.12±0.040.19±0.05##0.13±0.550.19±0.040.24±0.070.25±0.01
地黄饮子低剂量组110.12±0.040.16±0.04##0.21±0.54#0.19±0.040.24±0.080.25±0.04
步态指标n右前推进指数右后推进指数左前支撑时相/（s）左后支撑时相/（s）右前支撑时相/（s）右后支撑时相/（s）
正常组110.28±0.050.24±0.120.23±0.150.24±0.080.25±0.160.25±0.02
模型组110.35±0.130.36±0.04**0.25±0.080.35±0.05**0.33±0.16**0.23±0.04
阳性药组110.30±0.040.25±0.030.23±0.090.29±0.03#0.27±0.04#0.26±0.01
地黄饮子低剂量组110.28±0.04#0.25±0.07##0.25±0.010.24±0.070.24±0.070.22±0.03
地黄饮子低剂量组110.30±0.060.25±0.04##0.24±0.090.24±0.04##0.22±0.07##0.37±0.02
地黄饮子低剂量组110.29±0.05#0.25±0.07##0.30±0.010.24±0.06##0.24±0.06##0.35±0.02
), ArticleFig(id=1322928475484586353, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表5, caption=

地黄饮子对PD肾精虚证小鼠步态功能的影响（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
步态指标n左前肢接触面积/（m2）右前肢接触面积/（m2）左后肢接触面积/（m2）右后肢接触面积/（m2）左前推进时间/（s）左后推进指数/（s）
正常组110.13±0.030.16±0.060.17±0.060.19±0.560.23±0.120.25±0.06
模型组110.13±0.050.24±0.06**0.16±0.060.23±0.55*0.36±0.18**0.27±0.06
阳性药组110.10±0.020.25±0.040.14±0.010.21±0.030.24±0.080.25±0.03
地黄饮子低剂量组110.11±0.040.21±0.030.14±0.100.17±0.060.24±0.050.25±0.01
地黄饮子低剂量组110.12±0.040.19±0.05##0.13±0.550.19±0.040.24±0.070.25±0.01
地黄饮子低剂量组110.12±0.040.16±0.04##0.21±0.54#0.19±0.040.24±0.080.25±0.04
步态指标n右前推进指数右后推进指数左前支撑时相/（s）左后支撑时相/（s）右前支撑时相/（s）右后支撑时相/（s）
正常组110.28±0.050.24±0.120.23±0.150.24±0.080.25±0.160.25±0.02
模型组110.35±0.130.36±0.04**0.25±0.080.35±0.05**0.33±0.16**0.23±0.04
阳性药组110.30±0.040.25±0.030.23±0.090.29±0.03#0.27±0.04#0.26±0.01
地黄饮子低剂量组110.28±0.04#0.25±0.07##0.25±0.010.24±0.070.24±0.070.22±0.03
地黄饮子低剂量组110.30±0.060.25±0.04##0.24±0.090.24±0.04##0.22±0.07##0.37±0.02
地黄饮子低剂量组110.29±0.05#0.25±0.07##0.30±0.010.24±0.06##0.24±0.06##0.35±0.02
), ArticleFig(id=1322928475568472434, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组61.25±0.231.69±0.901.33±0.281.11±0.03
模型组60.74±0.22**1.09±0.26**0.88±0.16**1.36±0.06*
阳性药组60.85±0.221.31±0.13#1.10±0.26#1.27±0.04
地黄饮子低剂量组60.86±0.041.46±0.71##1.24±0.17##1.19±0.01
地黄饮子中剂量组60.94±0.12#1.32±0.66#1.25±0.13##1.43±0.19
地黄饮子高剂量组60.90±0.21#1.301±0.02#1.02±0.1.11#0.71±0.03#
), ArticleFig(id=1322928475648164211, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表6, caption=

GLUT1/β-Actin，GLUT3/β-Actin，GLUT4/β-Actin，GSK-3β/β-Actin mRNA相对表达比率（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组61.25±0.231.69±0.901.33±0.281.11±0.03
模型组60.74±0.22**1.09±0.26**0.88±0.16**1.36±0.06*
阳性药组60.85±0.221.31±0.13#1.10±0.26#1.27±0.04
地黄饮子低剂量组60.86±0.041.46±0.71##1.24±0.17##1.19±0.01
地黄饮子中剂量组60.94±0.12#1.32±0.66#1.25±0.13##1.43±0.19
地黄饮子高剂量组60.90±0.21#1.301±0.02#1.02±0.1.11#0.71±0.03#
), ArticleFig(id=1322928475732050292, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组61.25±0.051.05±0.171.18±0.201.28±0.42
模型组60.81±0.01**0.49±0.10**0.60±0.12*1.42±0.28*
阳性药组60.89±0.020.75±0.16#1.10±0.56#1.18±0.08#
地黄饮子低剂量组60.93±0.010.66±0.02#1.49±0.11##0.86±0.07##
地黄饮子中剂量组61.09±0.09#0.94±0.69##1.49±0.02##0.76±0.13##
地黄饮子高剂量组61.10±0.06#0.65±0.23#0.93±0.52#0.81±0.01##
), ArticleFig(id=1322928475828519285, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表7, caption=

GLUT1/β-Actin，GLUT3/β-Actin，GLUT4/β-Actin，GSK-3β/β-Actin mRNA相对表达比率（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组61.25±0.051.05±0.171.18±0.201.28±0.42
模型组60.81±0.01**0.49±0.10**0.60±0.12*1.42±0.28*
阳性药组60.89±0.020.75±0.16#1.10±0.56#1.18±0.08#
地黄饮子低剂量组60.93±0.010.66±0.02#1.49±0.11##0.86±0.07##
地黄饮子中剂量组61.09±0.09#0.94±0.69##1.49±0.02##0.76±0.13##
地黄饮子高剂量组61.10±0.06#0.65±0.23#0.93±0.52#0.81±0.01##
), ArticleFig(id=1322928475908211062, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组65.68±1.474.26±4.249.33±10.991.86±1.31
模型组61.64±3.58*3.56±2.243.69±0.56*7.13±6.28*
阳性药组62.50±1.453.50±2.562.78±2.315.15±4.92
地黄饮子低剂量组611.58±3.55##7.53±4.23#5.66±3.51#2.58±1.33#
地黄饮子中剂量组64.66±3.93#8.15±9.96#6.35±4.47#6.17±3.34
地黄饮子高剂量组621.97±2.42##4.01±1.693.14±2.925.81±3.30
), ArticleFig(id=1322928476004680055, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表8, caption=

GLUT1、GLUT3、GLUT4和GSK-3β蛋白在黑质中的表达情况（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组65.68±1.474.26±4.249.33±10.991.86±1.31
模型组61.64±3.58*3.56±2.243.69±0.56*7.13±6.28*
阳性药组62.50±1.453.50±2.562.78±2.315.15±4.92
地黄饮子低剂量组611.58±3.55##7.53±4.23#5.66±3.51#2.58±1.33#
地黄饮子中剂量组64.66±3.93#8.15±9.96#6.35±4.47#6.17±3.34
地黄饮子高剂量组621.97±2.42##4.01±1.693.14±2.925.81±3.30
), ArticleFig(id=1322928476084371832, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组614.95±10.831.11±0.813.39±2.037.75±11.16
模型组67.90±6.59**0.91±1.410.20±0.249*9.80±10.57
阳性药组69.88±6.183.36±4.43#1.49±0.415.04±3.66#
地黄饮子低剂量组611.57±7.45#3.01±3.110.52±0.595.17±4.27#
地黄饮子中剂量组621.91±8.35##10.15±5.52##0.75±0.5610.39±11.38
地黄饮子高剂量组613.20±11.42##5.04±3.99##2.77±1.37#5.72±3.97#
), ArticleFig(id=1322928476172452217, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, language=CN, label=表9, caption=

GLUT1、GLUT3、GLUT4和GSK-3β蛋白在纹状体中的表达情况（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nGLUT1GLUT3GLUT4GSK-3β
正常组614.95±10.831.11±0.813.39±2.037.75±11.16
模型组67.90±6.59**0.91±1.410.20±0.249*9.80±10.57
阳性药组69.88±6.183.36±4.43#1.49±0.415.04±3.66#
地黄饮子低剂量组611.57±7.45#3.01±3.110.52±0.595.17±4.27#
地黄饮子中剂量组621.91±8.35##10.15±5.52##0.75±0.5610.39±11.38
地黄饮子高剂量组613.20±11.42##5.04±3.99##2.77±1.37#5.72±3.97#
)], attaches=null, journal=Journal(id=1255846881855815682, delFlag=0, nameCn=中华中医药学刊, nameEn=Chinese Archives of Traditional Chinese Medicine, nameHistory1=null, nameHistory2=null, issn=1673-7717, eissn=null, cn=21-1546/R, coden=null, periodic=0, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=v4T+dd+NLAnioIpGAbkcEQ==, journalPrice=null, startedYear=null, abbrevIsoEn=Chinese Archives of Traditional Chinese Medicine, journalRemark=null, publicationField=null, createdTime=1777346829146, updatedTime=1788949222391, createdBy=18614031015, updatedBy=13041195026, firstLetterCn=Z, firstLetterEn=Z, subjectCode=Medical and Pharmaceutical Sciences, subjectName=null, subjectCodeEn=Medical and Pharmaceutical Sciences, subjectNameEn=null, picCn=v4T+dd+NLAnioIpGAbkcEQ==, picEn=RAy5vuC40hwJB+Y0pEARug==, jcr=null, cjcr=null, exts=[JournalExt(id=1304510846391050374, language=CN, name=中华中医药学刊, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1788949222419, updatedTime=1788949222419, createdBy=13041195026, updatedBy=13041195026, submissionGuidelinesUrl=, submissionAuthorUrl=https://zyhs.cbpt.cnki.net/index.aspx?t=1, submissionEditorUrl=https://zyhs.cbpt.cnki.net/index.aspx?t=3, submissionReviewUrl=https://zyhs.cbpt.cnki.net/index.aspx?t=2, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1304510846449770631, language=EN, name=Chinese Archives of Traditional Chinese Medicine, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1788949222433, updatedTime=1788949222433, createdBy=13041195026, updatedBy=13041195026, submissionGuidelinesUrl=, submissionAuthorUrl=https://zyhs.cbpt.cnki.net/index.aspx?t=1, submissionEditorUrl=https://zyhs.cbpt.cnki.net/index.aspx?t=3, submissionReviewUrl=https://zyhs.cbpt.cnki.net/index.aspx?t=2, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1255847919539208197, websiteList=[Website(id=1255847989868900719, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1255847919539208197, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/zhzyyxk/CN, language=CN, createTime=1777347093312, createBy=18614031015, updateTime=1777347427646, updateBy=18614031015, name=中华中医药学刊-中文, tplId=1146099689490845704, title=中华中医药学刊, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1255849512594170105, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=articleTextType, value=kx, createTime=1777347456358, updateTime=1777347456358, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512564809974, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=banner, value=null, createTime=1777347456352, updateTime=1777347456352, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512631918844, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=grayFlag, value=0, createTime=1777347456367, updateTime=1777347456367, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512552227061, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=logo, value=https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/file/pic?fileId=uitCA2DBwhJaQSiSV07uhw==, createTime=1777347456348, updateTime=1777347456348, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512657084670, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=minRunFlag, value=0, createTime=1777347456373, updateTime=1777347456373, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512589975800, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/file/pic, createTime=1777347456357, updateTime=1777347456357, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512648696061, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=silenceFlag, value=0, createTime=1777347456371, updateTime=1777347456371, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512581587191, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1777347456355, updateTime=1777347456355, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512619335930, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=themeColor, value=null, createTime=1777347456364, updateTime=1777347456364, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849512627724539, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989868900719, code=themeStyle, value=null, createTime=1777347456366, updateTime=1777347456366, creator=18614031015, updator=18614031015)]), Website(id=1255847989944398211, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1255847919539208197, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/zhzyyxk/EN, language=EN, createTime=1777347093330, createBy=18614031015, updateTime=1777347417860, updateBy=18614031015, name=中华中医药学刊-英文, tplId=1146101810881728533, title=Chinese Archives of Traditional Chinese Medicine, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1255849538993119491, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=articleTextType, value=kx, createTime=1777347462652, updateTime=1777347462652, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849538972147968, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=banner, value=null, createTime=1777347462647, updateTime=1777347462647, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849539047645446, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=grayFlag, value=0, createTime=1777347462665, updateTime=1777347462665, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849538930204927, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=logo, value=https://castjournals.cast.org.cn/joweb/zhzyyxk/EN/file/pic?fileId=uitCA2DBwhJaQSiSV07uhw==, createTime=1777347462637, updateTime=1777347462637, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849539064422664, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=minRunFlag, value=0, createTime=1777347462669, updateTime=1777347462669, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849538988925186, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zhzyyxk/EN/file/pic, createTime=1777347462651, updateTime=1777347462651, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849539060228359, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=silenceFlag, value=0, createTime=1777347462668, updateTime=1777347462668, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849538980536577, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1777347462649, updateTime=1777347462649, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849539001508100, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=themeColor, value=null, createTime=1777347462654, updateTime=1777347462654, creator=18614031015, updator=18614031015), WebsiteProps(id=1255849539039256837, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1255847989944398211, code=themeStyle, value=null, createTime=1777347462663, updateTime=1777347462663, creator=18614031015, updator=18614031015)])], journalTitle=中华中医药学刊, weixinUrl=null, journalUrl=https://castjournals.cast.org.cn/zhzyyxk, iacademicId=null, status=1, seqNo=null, journalTitleEn=Chinese Archives of Traditional Chinese Medicine, journalPhotoCn=v4T+dd+NLAnioIpGAbkcEQ==, journalPhotoEn=RAy5vuC40hwJB+Y0pEARug==, journalFirstLetter=Z, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false, interPubPlatform=, interPubPlatformUrl=null), detailUrlCn=https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2025.11.023, detailUrlEn=https://castjournals.cast.org.cn/joweb/zhzyyxk/EN/10.13193/j.issn.1673-7717.2025.11.023, pdfUrlCn=https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/PDF/10.13193/j.issn.1673-7717.2025.11.023, pdfUrlEn=https://castjournals.cast.org.cn/joweb/zhzyyxk/EN/PDF/10.13193/j.issn.1673-7717.2025.11.023, aliStartDate=0, aliEndDate=0, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=1, orderTime=1762704000000, fullTextJson=null, articleText=null, reference=null)
收藏切换
基于糖代谢的帕金森病肾精虚证生物学机制及地黄饮子的干预作用研究
收藏切换
PDF下载
赵雅飞 , 韩诚 , 赵玉婷 , 李少创 , 青千裕 , 赵琼
中华中医药学刊 | 国家项目点击 2025,43(11): 107-116
收起
收藏切换
中华中医药学刊 |国家项目点击 2025 , 43 (11) : 107 -116
基于糖代谢的帕金森病肾精虚证生物学机制及地黄饮子的干预作用研究
全屏
[Author(id=1322928466424889639, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928466517164329, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466424889639, language=EN, stringName=Yafei ZHAO, firstName=Yafei, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928466622021930, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466424889639, language=CN, stringName=赵雅飞, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio={"content":"

赵雅飞（1994-），女，河南平顶山人，硕士，研究方向：藏象理论。

"}, bioImg=null, bioContent=

赵雅飞（1994-），女，河南平顶山人，硕士，研究方向：藏象理论。

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928466726879532, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928466823348526, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466726879532, language=EN, stringName=Cheng HAN, firstName=Cheng, middleName=null, lastName=HAN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928466894651695, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466726879532, language=CN, stringName=韩诚, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928466970149169, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928467058229555, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466970149169, language=EN, stringName=Yuting ZHAO, firstName=Yuting, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928467150504244, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928466970149169, language=CN, stringName=赵玉婷, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928467221807414, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928467293110584, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467221807414, language=EN, stringName=Shaochuang LI, firstName=Shaochuang, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928467368608057, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467221807414, language=CN, stringName=李少创, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928467439911227, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322928467540574525, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467439911227, language=EN, stringName=Qianyu QING, firstName=Qianyu, middleName=null, lastName=QING, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928467628654910, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928467439911227, language=CN, stringName=青千裕, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])]), Author(id=1322928469297987904, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=413568433@qq.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322928469402845506, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928469297987904, language=EN, stringName=Qiong ZHAO, firstName=Qiong, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322928469490925891, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, authorId=1322928469297987904, language=CN, stringName=赵琼, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=山西中医药大学，山西 太原 030619, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322928466257117475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, xref=null, ext=[AuthorCompanyExt(id=1322928466269700388, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China), AuthorCompanyExt(id=1322928466278088997, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322928457453273330, companyId=1322928466257117475, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=山西中医药大学，山西 太原 030619)])])]
赵雅飞, 韩诚, 赵玉婷, 李少创, 青千裕, 赵琼
作者信息
  • 山西中医药大学，山西 太原 030619
通讯作者:
赵琼（1979-），女，山西晋中人，副教授，硕士研究生导师，博士，研究方向：藏象理论。E-mail：。
作者简介:

赵雅飞（1994-），女，河南平顶山人，硕士，研究方向：藏象理论。

Research on Biological Mechanism of PD of Kidney Essence Deficiency Syndrome Based on Glucose Metabolism and Intervention Effect of Dihuang Yinzi（地黄饮子）
Yafei ZHAO, Cheng HAN, Yuting ZHAO, Shaochuang LI, Qianyu QING, Qiong ZHAO
Affiliations
  • Shanxi University of Chinese Medicine，Taiyuan 030619，Shanxi，China
出版时间: 2025-11-10 doi: 10.13193/j.issn.1673-7717.2025.11.023
文章导航
收藏切换
摘要
收起
目的

从糖代谢层面探讨帕金森病（Parkinson's disease，PD）肾精虚证的生物学机制和地黄饮子干预帕金森病肾精虚证的作用机制。

方法

采用SPF级雄性12周龄的SAM-P8小鼠55只，分为模型组、阳性药组、地黄饮子低剂量组、地黄饮子中剂量组、地黄饮子高剂量组每组11只和SAM-R1小鼠11只作为正常组，SAM-P8小鼠腹腔注射1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-Methyl-4-phenyl-1，2，3，6-tetrahydropyridine，MPTP）（30 mg/kg，1次/d）7 d建立PD模型，地黄饮子干预4周。观察小鼠一般状态指标，测定小鼠空腹血糖值、行为学指标。采用HE染色观察小鼠肾脏及睾丸组织结构变化，采用蛋白免疫印迹法（Western blot，WB）、免疫组化法、聚合酶链式反应（Polymerase chain reaction，PCR）检测小鼠脑组织中黑质、纹状体葡萄糖转运蛋白1（Glucose transporter 1，GLUT 1）、葡萄糖转运蛋白3（Glucose transporter 3，GLUT 3）、葡萄糖转运蛋白4（Glucose transporter 4，GLUT 4）、糖原合成激酶3β（Glycogen synthase kinase-3β，GSK-3β）蛋白含量。

结果

在旷场实验中，与正常组相比，模型组小鼠运动总路程减少（P<0.05），潜伏期增加（P<0.05）；与模型组相比，地黄饮子低、高剂量组小鼠潜伏期降低（P<0.05）；地黄饮子中剂量组小鼠总路程增加（P<0.05）。在爬杆实验中，与正常组比较，模型组爬杆时间增加（P<0.05）；与模型组相比，地黄饮子低、高剂量组时间降低（P<0.05）；与给药前相比，地黄饮子低、中、高剂量组时间降低（P<0.05）。在步态实验中，与正常组相比，模型组小鼠右前接触面积、左前推进时间、右后推进指数、左后支撑时相、右前支撑时相差异有统计学意义（P<0.01）；与模型组比较，地黄饮子低剂量组小鼠右后推进指数差异有统计学意义（P<0.01），地黄饮子中剂量组小鼠右前肢接触面积、右后推进指数、左后支撑时相、右前支撑时相差异有统计学意义（P<0.01），地黄饮子高剂量组小鼠右前肢接触面积、左后支撑时相、右前支撑时相差异有统计学意义（P<0.01）。HE肾脏染色检测结果：与正常组相比，模型组出现肾小球囊上皮细胞增生、脂滴增加、肾小管扩张、细胞碎片增加、红细胞增加、淋巴细胞增加、成纤维细胞增加、纤维细胞增加等病理改变。与模型组相比，地黄饮子高剂量组出现脂滴降低、红细胞降低、纤维细胞降低。HE睾丸染色结果显示：与正常组相比，模型组见生精上皮空泡化、精子数量减少等病变现象。与模型组相比，地黄饮子高剂量组出现生精上皮空泡化减轻。Westernblot检测结果：与正常组相比，模型组小鼠黑质GLUT1蛋白表达显著降低（P<0.01），GLUT3和GLUT4蛋白表达降低（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1蛋白表达显著增加（P<0.01），GLUT4蛋白表达增加（P<0.05），GSK-3β蛋白表达降低（P<0.05）。与正常组相比，模型组小鼠纹状体GLUT1和GLUT3蛋白表达显著降低（P<0.01），GLUT4蛋白表达降低（P<0.05），GSK-3β蛋白表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1蛋白表达增高（P<0.05），GLUT3蛋白表达显著增高（P<0.01），GLUT4蛋白表达升高（P<0.05），GSK-3β蛋白表达降低（P<0.05）。实时荧光定量PCR检测结果：与正常组相比，模型组小鼠黑质GLUT1、GLUT3、GLUT4 mRNA表达显著降低（P<0.01），GSK-3β表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1、GLUT3、GLUT4表达增高（P<0.05），GSK-3β表达降低（P<0.05）。与正常组相比，模型组小鼠纹状体GLUT1和GLUT3 mRNA表达显著降低（P<0.01），GLUT4表达降低（P<0.05），GSK-3β表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1、GLUT3、GLUT4表达增高（P<0.05），GSK-3β表达降低（P<0.05）。免疫组化检测结果：与正常组相比，模型组小鼠黑质GLUT1、GLUT4的表达降低（P<0.05），GSK-3β表达升高（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1表达显著升高（P<0.01）。与正常组相比，模型组小鼠纹状体GLUT1表达显著降低（P<0.01），GLUT4表达降低（P<0.05）。与模型组相比，地黄饮子高剂量组GLUT1、GLUT3表达显著增高（P<0.01），GLUT4表达升高（P<0.05），GSK-3β表达降低（P<0.05）。

结论

①地黄饮子能够提高PD肾精虚证小鼠运动速度、改善抓握能力、增强四肢协调性、增强对新环境的探索能力。②地黄饮子能够降低PD肾精虚证小鼠空腹血糖，通过纠正糖代谢，改善机体能量代谢。③地黄饮子能够提高PD肾精虚证小鼠脑黑质GLUT1、GLUT4蛋白的表达，降低脑黑质GSK-3β蛋白的表达，提高脑纹状体GLUT1、GLUT3、GLUT4的表达，降低脑纹状体GSK-3β蛋白的表达，地黄饮子中、高剂量组效果高于地黄饮子低剂量组。④帕金森病肾精虚证存在GLUT1、GLUT3、GLUT4、GSK-3β蛋白的摄入异常，地黄饮子可以通过调节帕金森病小鼠黑质、纹状体中GLUT1、GLUT3、GLUT4、GSK-3β蛋白的表达，治疗帕金森病肾精虚证。

帕金森病  /  肾精虚证  /  糖代谢  /  地黄饮子  /  葡萄糖转运蛋白
Objective

To explore the biological mechanism of Parkinson's disease（PD）of kidney essence deficiency syndrome from the perspective of glucose metabolism and the mechanism of intervention of Dihuang Yinzi（地黄饮子）in PD of kidney essence deficiency syndrome.

Methods

Fifty-five SPF grade male 12-week-old SAM-P8 mice were divided into model group，positive drug group，Dihuang Yinzi low，middle and high dose groups，with 11 mice in each group，and 11 SAM-R1 mice were as the normal group. The PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine（MPTP）（30 mg/kg，once a day）into SAM-P8 mice for 7 days，and the intervention lasted for 4 weeks. The general status indicators of mice was observed，and the fasting blood glucose levels and behavioral indicators in mice were measured. HE staining was used to observe the structural changes of mouse kidney and testis. Western blot（WB），immunohistochemistry and polymerase chain reaction（PCR）were used to detect the protein contents of glucose transporter 1（GLUT1），glucose transporter 3（GLUT3），glucose transporter 4（GLUT4），and glycogen synthase kinase 3β（GSK-3β）in the substantia nigra and striatum of mouse brain tissue.

Results

In the open field experiment，compared with the normal group，the model group showed a decrease in total exercise distance（P<0.05）and an increase in latency（P<0.05）. Compared with that of the model group，the latency of mice in the Dihuang Yinzi low and high dose groups decreased（P<0.05）. The total distance of mice in the Dihuang Yinzi middle dose group increased（P<0.05）. In the pole climbing experiment，compared with the normal group，the model group showed an increase in pole climbing time（P<0.05）. Compared with the model group，the Dihuang Yinzi low and high groups showed a decrease in time（P<0.05）. Compared with those before administration，the Dihuang Yinzi low，middle and high dose groups showed a decrease in time（P<0.05）. In the gait experiment，compared with the normal group，the model group showed significant differences in right anterior contact area，left anterior propulsion time，right posterior propulsion index，left posterior support phase and right anterior support phase（P<0.01）. Compared with that in the model group，there was a significant difference in the right posterior propulsion index（P<0.01）in the Dihuang Yinzi low dose group. There were significant differences in the contact area of the right forelimb，right posterior propulsion index，left posterior support phase，and right anterior support phase in the Dihuang Yinzi middle dose group（P<0.01）. There were significant differences in the contact area of the right forelimb，left posterior support phase and right anterior support phase in the Dihuang Yinzi high dose group（P<0.01）. HE renal staining test results showed compared with the blank group，the model group showed pathological changes such as glomerular epithelial cell proliferation，increased lipid droplets，renal tubular dilation，increased cell debris，increased red blood cells，increased lymphocytes，increased fibroblasts and increased fibroblasts. Compared with the model group，the Dihuang Yinzi high dose group showed a decrease in lipid droplets，red blood cells and fibroblasts. The HE testicular staining results showed that compared with the blank group，the model group showed pathological changes such as vacuolization of the spermatogenic epithelium and decreased sperm count. Compared with the model group，the Dihuang Yinzi high dose group showed reduced vacuolization of the spermatogenic epithelium. WB detection results showed compared with the normal group，the model group showed a significant decrease in GLUT1 protein expression in the substantia nigra（P<0.01），and a decrease in protein expressions of GLUT3 and GLUT4（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed a significant increase in protein expressions of GLUT1 and GLUT4 protein expression（P<0.01，P<0.05）and GSK-3βprotein expression decreased（P<0.05）. Compared with the normal group，the protein expressions of GLUT1 and GLUT3 in the striatum of the model group decreased significantly（P<0.01），and the expression of GLUT4 protein decreased（P<0.05）. The protein expression of GSK-3βincreased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed an increase in protein expression of GLUT1，GLUT3 and GLUT4（P<0.05，P<0.01），and GSK-3βprotein expression decreased（P<0.05）. Real time fluorescence quantitative PCR detection results showed compared with the normal group，the mRNA expressions of GLUT1，GLUT3 and GLUT4 in the substantia nigra of the model group mice were significantly reduced（P<0.01），and GSK-3βexpression increased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed increased expressions of GLUT1，GLUT3 and GLUT4（P<0.05），and GSK-3βexpression decreased（P<0.05）. Compared with the normal group，the mRNA expressions of GLUT1 and GLUT3 in the striatum of the model group were significantly lower（P<0.01），the expression of GLUT4 was lower（P<0.05）and the expression of GSK-3βincreased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group showed increased expressions of GLUT1，GLUT3 and GLUT4（P<0.05），and GSK-3βexpression decreased（P<0.05）. Immunohistochemical test results showed compared with the normal group，the expressions of GLUT1 and GLUT4 in the substantia nigra of the model group decreased（P<0.05），and GSK-3βexpression increased（P<0.05）. Compared with the model group，the Dihuang Yinzi high dose group significantly increased the expression of GLUT1（P<0.01）. Compared with the normal group，the expressions of GLUT1 and GLUT4 in the striatum of the model group decreased significantly（P<0.01，P<0.05），respectively. Compared with the model group，the Dihuang Yinzi high dose group significantly increased the expressions of GLUT1，GLUT3 and GLUT4（P<0.01，P<0.05），and the expression of GSK-3βdecreased（P<0.05）.

Conclusion

1. Dihuang Yinzi can improve the motor speed，grip ability，limb coordination and exploration ability of PD mice with kidney essence deficiency syndrome.2. Dihuang Yinzi can reduce fasting blood glucose in mice with PD kidney essence deficiency syndrome，improve energy metabolism by correcting glucose metabolism.3. Dihuang Yinzi can increase the protein expressions of GLUT1 and GLUT4 in the substantia nigra of PD mice with kidney essence deficiency syndrome，and reduce the protein expression of GSK-3βin the substantia nigra of the brain，increase the expressions of GLUT1，GLUT3 and GLUT4 in the brain striatum，and reduce the expression of GSK-3β in the brain striatum. The protein expression in the Dihuang Yinzi middle and high dose groups was higher than that in the Dihuang Yinzi low dose group.4. Dihuang Yinzi has abnormal intake of GLUT1，GLUT3，GLUT4 and GSK-3βproteins. Dihuang Yinzi can treat PD of kidney essence deficiency syndrome by regulating the expressions of GLUT1，GLUT3，GLUT4 and GSK-3β proteins in the substantia nigra and striatum of PD mice.

Parkinson's disease  /  kidney essence deficiency syndrome  /  sugar metabolism  /  Dihuang Yinzi（地黄饮子）  /  glucose transporter protein
赵雅飞, 韩诚, 赵玉婷, 李少创, 青千裕, 赵琼. 基于糖代谢的帕金森病肾精虚证生物学机制及地黄饮子的干预作用研究. 中华中医药学刊, 2025 , 43 (11) : 107 -116 . DOI: 10.13193/j.issn.1673-7717.2025.11.023
Yafei ZHAO, Cheng HAN, Yuting ZHAO, Shaochuang LI, Qianyu QING, Qiong ZHAO. Research on Biological Mechanism of PD of Kidney Essence Deficiency Syndrome Based on Glucose Metabolism and Intervention Effect of Dihuang Yinzi（地黄饮子）[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (11) : 107 -116 . DOI: 10.13193/j.issn.1673-7717.2025.11.023
正文
收起
帕金森病（Parkinson's disease，PD）是一种常见的中枢神经系统疾病，常伴有运动迟缓、静止性震颤、认知功能障碍等症状[1]。其病理特点主要为黑质致密部多巴胺能神经元的缺失、多巴胺能神经元区路易小体、多脑区路易神经突增多[2]。至今，PD治疗仍然以药物为主，主要包括左旋多巴、N-甲基-D-天冬氨酸（N-methyl-D-aspartic acid，NMDA）受体阻滞剂、抗胆碱能药物[3]。这类药物可有效缓解PD的症状，但长期使用可能会带来一系列不良反应。葡萄糖和能量代谢的改变是PD的早期分子事件，是发病的潜在危险因素因此，越来越多的研究关注于代谢异常和神经退行性变的关系，帕金森病糖代谢情况渐渐成为了大家关注的重点。
中医将PD归属于“颤证”范畴，中医药在防治PD方面具有丰富的临床经验。PD多发于中老年人，高发于55岁以上人群，从中医角度思考，此年龄段是人体各脏腑功能减退的阶段，以肾中精气发展至由盛至亏虚为主要生理特点。地黄饮子为滋肾阴、补肾阳、开窍化痰之要方，现代药理学的研究证实，地黄饮子能够提高胆碱能系统活性、改善脑组织能量代谢、提高学习记忆能力、保护神经元[4]。因此，地黄饮子在防治帕金森病方面有着巨大的潜力。
糖代谢异常是PD的一个重要病理机制，脑的正常功能活动依赖从血液中不断提供的葡萄糖来维持。在脑内能量代谢过程中，葡萄糖是首要的能量来源，脑组织的代谢特点使其必须依赖于葡萄糖的摄取来维持正常的活动。肾精虚证是PD的重要病机，肾藏精生髓，脑为髓海，主神志，髓由肾精及气血化生，充养其脑，肾精亏虚则精不上承，脑髓空虚而脑失所养。本研究旨在探讨糖代谢异常是否为PD肾精虚证的机制，地黄饮子补肾益精治疗PD的作用机制是否通过调整大脑糖代谢异常实现。在本研究中，建立PD模型小鼠通过行为学观察和检测血糖值等指标，评估地黄饮子对PD肾精虚证和糖代谢异常的干预效果。同时，检测地黄饮子对糖代谢相关蛋白表达的影响，探讨其可能的作用机制。希望本研究的相关结果能为明确PD的发病机制和中医药补肾治疗神经退行性脑病提供新的思路和方向。
1　实验材料
收起
1.1　实验动物
SPF级雄性12周龄SAM-P8小鼠55只，体质量（29±3）g，SPF级雄性12周龄SAM-R1小鼠11只，体质量（28±2）g，购自北京大学医学部，合格证编号：110332220100020352，许可证号：SCXK（京）2021-0013，经山西中医药大学伦理委员会批准，按国际动物实验方针进行科学实验。
受试动物饲养于山西中医药大学科研中心SPF级动物房。饲养室环境温度控制在（22±2）℃，相对湿度40% ～60%，自然光照，通风良好。动物自由饮食、进水及活动。
1.2　试剂与仪器
全自动多色荧光及化学发光凝胶成像系统（北京赛智创业科技有限公司，ChampChemi Professional），电泳仪（北京六一生物科技有限公司，DYY-6D），声波细胞粉碎机（宁波新芝生物科技股份有限公司，JY92-IIN），光学显微镜（奥林巴斯有限公司，BX53），1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-Methyl-4-phenyl-1，2，3，6-tetrahydropyridine，MPTP）（广州市鲁诚生物科技有限公司，SLBM9246V），β-actin抗体（ab8226，英国Abcam公司），anti-糖原合成激酶3β（Glycogen synthase kinase-3β，GSK-3β）antibody（华安生物，EET1607-71），anti-Glucose Tran sporter葡萄糖转运蛋白4（Glucose transporter 4，GLUT 4），Mouse Monoclonal Antibody（华安生物，M1505-6），葡萄糖转运蛋白3（Glucose transporter 3，GLUT 3）Rabbit mAb（武汉博士德生物工程有限公司，A4137），anti-葡萄糖转运蛋白1（Glucose transporter 1，GLUT 1）Antibody（武汉博士德生物工程有限公司，PB9435）。
2　实验方法
收起
2.1　实验分组
SPF级雄性SAM-P8小鼠55只，适应性喂养1周后，按照rand函数随机分为模型组、地黄饮子低剂量组、地黄饮子中剂量组、地黄饮子高剂量组、阳性药组，每组11只。SPF级雄性SAM-R1小鼠11只作为正常组。小鼠在实验期间自由进食和饮水。
2.2　试剂配制及给药方式
2.2.1　地黄饮子水煎剂制备
熟地黄12 g，巴戟天9 g，山茱萸9 g，石斛9 g，肉苁蓉9 g，炮附子6 g，五味子6 g，官桂6 g，白茯苓6 g，麦门冬6 g，石菖蒲6 g，远志6 g，薄荷3 g，购自北京同仁堂晋中药店有限责任公司安宁店。煎煮前每剂药加500 mL纯水浸泡2 h（薄荷后下，附子先煎）[5]，煮沸后转为文火煮30 min。滤出药液后再加等量清水依上法再次煎煮，将两次取出的药液混合（过程中加入薄荷），每副药物浓缩成46.5 mL。4℃冰箱保存，并在使用前回温并充分摇匀。给药1次/d，持续给药1个月。
2.2.2　盐酸美金刚混悬液制备
将盐酸美金刚片放入研钵研磨成粉末，加入纯水，制成混悬液，浓度为0.4 mg/（mL·d），持续给药1个月。
2.2.3　给药方式
各组详细给药剂量和方法见表1。
2.3　模型制备
采用SAM-P8小鼠，MPTP腹腔注射建立PD肾精虚证模型，连续7 d，浓度为30 mg/kg，1次/d。MPTP采用灭菌的纯水溶解配制，现配现用，根据小鼠体质量计算腹腔注射用量[6]。
2.4　检测指标及方法
2.4.1　空腹血糖值
于给药后的第7、14、21、28、35、42、49、56天，12 h禁食不禁水，尾静脉取血，测定空腹血糖值[7]。
2.4.2　行为学观察
（1）步态分析实验：步态分析实验用于评价动物的运动能力和协调性。于实验开始前3 d，各组小鼠每天进行1次训练。使用DigiGait动物步态检测分析系统，在检测过程中，将小鼠置于平台中，使用高频摄像机记录连续10 s的步态行为。录制完成的视频通过计算机分析软件分析，评价动物平衡协调能力。每只小鼠重复检测3次，每次间隔至少10 min，取平均值进行分析。
（2）爬杆实验：爬杆实验[8]用于检测模型小鼠的运动功能。自制一根高50 cm，直径2.5 cm，顶端装有直径25 cm小球的不锈钢杆，用胶布将小球及杆包裹起来防止打滑。检测时，将小鼠头部朝上放于杆顶部位置，检测并记录小鼠爬下的时间，以小鼠双前肢接触底部平台为爬完全长。实验前让小鼠进行爬杆训练1次，实验时连续测定3次，取平均值。
（3）旷场实验：旷场实验[9]使用SuperMaze动物行为学视频分析软件评价小鼠的自主活动能力。实验时，在相对安静的环境下，将小鼠放入测试箱（40 cm×40 cm×40 cm）中央，四周黑色，底部浅灰色。适应3 min后开始检测，计算机自动检测小鼠5 min内在测试箱中的自发活动情况，并获取小鼠的运动轨迹，每次更换老鼠时使用酒精棉球擦拭清除敞箱内异物，祛除气味干扰，测试3次取平均值。
2.4.3　指标检测
（1）样品采集：行为学实验结束后，每组随机取3只，异氟烷麻醉后经心尖部灌注常温生理盐水（50 mL）和4%多聚甲醛（30 mL），断头取脑，取肾脏、睾丸，放入含有4%多聚甲醛的离心管中备用。余下小鼠异氟烷麻醉后断头取脑，参照ALLEN BRAIN ATLAS在线图谱和Karunakaran等的方法分离黑质部位脑组织，将其冷冻在液氮中，保存在-80℃中，用于蛋白免疫印迹法（Western blot，WB）和实时荧光定量聚合酶链式反应（Polymerase chain reaction，PCR）检测使用。
（2）WB检测PD肾精虚证小鼠黑质、纹状体GLUT1、GLUT3、GLUT4、GSK-3β蛋白含量：分别提取PD小鼠黑质、纹状体的蛋白，取少量蛋白用于BCA法蛋白定量，剩余蛋白各加入1/4体积的5×loadingbuffer，100℃沸水煮10 min使蛋白变性。根据蛋白浓度计算各样品上样量，经相应浓度SDSPAGE凝胶电泳分离蛋白后，转膜，3%BSA封闭蛋白条带，之后加入相应的一抗及二抗进行免疫反应，滴加超敏发光液经ECL显色后，用GelPro31进行蛋白条带灰度分析。
（3）实时荧光定量PCR检测PD肾精虚证小鼠黑质、纹状体GLUT1、GLUT3、GLUT4、GSK-3β蛋白含量：①模板DNA的变性：将含有目标DNA的样品加入PCR反应管中，然后将管子置于热板上，并加热到95℃以上，使DNA的双链结构解开成单链的DNA模板。②引物的结合：将PCR反应管降温到50～60℃时，引物（由两段寡核苷酸组成的DNA序列）与模板DNA序列相互作用，使它们结合成双链结构。③DNA聚合酶的作用：将PCR反应管的温度升高到72℃时，DNA聚合酶开始作用，它将在引物的基础上复制模板DNA序列，产生1个新的DNA分子。④重复循环：以上3个步骤构成1个PCR循环，每个循环可以扩增模板DNA的数量翻倍。PCR循环可以重复30～40次，从而产生数以百万计的DNA复制品。⑤最终延伸：最后，PCR反应管中的DNA链伸长过程结束，将反应体制加热到72℃以上，保持5～10 min，使其完成最终延伸。序列信息见表2。
（4）免疫组化染色检测PD肾精虚证小鼠黑质、纹状体GLUT1、GLUT3、GLUT4、GSK-3β蛋白含量：各组取6只小鼠经心脏灌流后，取脑，沉蔗糖，冰冻切片，按照常规免疫组化步骤进行封闭、一抗、二抗孵育、封片。共聚焦显微镜下观察，用ImageProPlus6.0进行阳性染色面积及密度的统计。
（5）苏木精-伊红（HE）染色观察肾脏及睾丸组织结构变化：HE染色观察肾脏及睾丸组织结构变化：肾脏及睾丸钙后，脱水、石蜡包埋，之后进行HE染色，于光学显微镜下观察病理变化，并进行Mankin评分。
2.5　统计学方法
采用GraphPad Prism5.0统计软件进行数据分析，计量资料用表示，两两比较采用t检验，组间比较用单因素方差分析（ANOVA），以P<0.05为差异有统计学意义。
3　结果
收起
3.1　小鼠空腹血糖值检测结果
如图1所示，与正常组相比，模型组小鼠造模后、给药第1、4周空腹血糖升高，差异有统计学意义（P<0.05）；与模型组相比，阳性药组小鼠给药第3、4周空腹血糖降低，地黄饮子低剂量组小鼠造模后、给药第3周空腹血糖降低，地黄饮子中剂量组小鼠给药第3周空腹血糖降低，地黄饮子高剂量组小鼠给药第2、3、4周空腹血糖降低，差异均有统计学意义（P<0.05）。与给药前相比，给药第2周地黄饮子高剂量组，给药第3周地黄饮子低、高剂量组空腹血糖降低，给药第4周阳性药组、地黄饮子低、中、高剂量组空腹血糖降低，差异均有统计学意义（P<0.05）。
3.2　小鼠行为学结果检测结果
3.2.1　旷场实验检测结果
地黄饮子对小鼠旷场中移动总路程、潜伏期、平均速度、静止时间、跨格次数的影响如表3所示。与正常组相比，模型组小鼠运动总路程减少，潜伏期增加，差异均有统计学意义（P<0.05）。与模型组相比，地黄饮子低、高剂量组小鼠潜伏期降低，地黄饮子中剂量组小鼠总路程增加，差异均有统计学意义（P<0.05）。各组小鼠的平均速度、静止时间、跨格次数各项指标差异均无统计学意义（P>0.05）。
3.2.2　爬杆实验
如表4所示，在爬杆实验中，与正常组比较，模型组爬杆时间增加；与模型组相比，地黄饮子低、高剂量组给药后爬杆时间降低；与给药前相比，地黄饮子低、中、高剂量组爬杆时间降低，差异均有统计学意义（P<0.05）。
3.2.3　步态实验检测结果
如表5所示，与正常组相比，模型组小鼠的右前接触面积、左前推进时间、右后推进指数、左后支撑时相、右前支撑时相差异有显著统计学意义（P<0.01），右后肢接触面积差异有统计学意义（P<0.05）。与模型组比较，阳性药组小鼠的左后支撑时相、右前支撑时相差异有统计学意义（P<0.05）；地黄饮子低剂量组小鼠的右后推进指数差异有显著统计学意义（P<0.01），右前推进指数差异有统计学意义（P<0.05）；地黄饮子中剂量组小鼠的右前肢接触面积、右后推进指数、左后支撑时相、右前支撑时相差异有显著统计学意义（P<0.01），地黄饮子高剂量组小鼠的右前肢接触面积、左后支撑时相、右前支撑时相有差异有显著统计学意义（P<0.01），右前推进指数差异有统计学意义（P<0.05）。
3.3　小鼠肾脏、睾丸HE染色结果
3.3.1　小鼠肾脏HE染色结果
肾脏HE染色结果如插页ⅩⅩⅢ图2所示：与正常组相比，模型组出现肾小球囊上皮细胞增生、脂滴增加、肾小管扩张、细胞碎片增加、红细胞增加、淋巴细胞增加、成纤维细胞增加、纤维细胞增加等病理改变。与模型组相比，阳性药组出现脂滴降低、红细胞降低；地黄饮子低剂量组出现脂滴降低、红细胞降低；地黄饮子中剂量组出现红细胞降低、成纤维细胞降低；地黄饮子高剂量组出现脂滴降低、红细胞降低、纤维细胞降低。这一结果表明，肾精虚证小鼠模型建立成功，地黄饮子可以改善炎性细胞浸润和纤维组织增生，扭转肾损伤。
3.3.2　小鼠睾丸HE染色结果
睾丸HE染色结果如插页ⅩⅩⅣ图3所示：与正常组相比，模型组见生精上皮空泡化、精子数量减少等病变现象。与模型组相比，地黄饮子低剂量组出现生精上皮空泡化减轻，地黄饮子中剂量组出现精子数量增加，地黄饮子高剂量组出现生精上皮空泡化减轻。这一结果表明，地黄饮子可以相对减轻睾丸组织病变程度。
3.4　Western Blot检测结果
3.4.1　Western Blot法检测黑质中GLUT1、GLUT3、GLUT4和GSK-3β蛋白的表达
结果如图4所示，与正常组相比，模型组小鼠黑质GLUT1蛋白表达显著降低，差异有显著统计学意义（P<0.01），GLUT3和GLUT4蛋白表达降低，差异有统计学意义（P<0.05）。与模型组相比，阳性药组GLUT1蛋白表达显著增加，差异有显著统计学意义（P<0.01）；地黄饮子低剂量组GLUT1蛋白表达显著增加，差异有显著统计学意义（P<0.01），GLUT4和GSK-3β表达升高，差异有统计学意义（P<0.05）；地黄饮子中剂量组GLUT1蛋白表达显著升高，差异有显著统计学意义（P<0.01），GLUT4蛋白表达升高，差异有统计学意义（P<0.05）；地黄饮子高剂量组GLUT1蛋白表达显著增加，差异有显著统计学意义（P<0.01），GLUT4蛋白表达增加，GSK-3β蛋白表达降低，差异均有统计学意义（P<0.05）。
3.4.2　Western Blot法检测对小鼠纹状体中GLUT1、GLUT3、GLUT4和GSK-3β蛋白表达的影响
结果如图5所示，与正常组相比，模型组小鼠纹状体GLUT1和GLUT3蛋白表达显著降低，差异有显著统计学意义（P<0.01），GLUT4蛋白表达降低，GSK-3β蛋白表达升高，差异均有统计学意义（P<0.05）。与模型组相比，阳性药组GLUT3蛋白表达增加，GSK-3β蛋白表达降低，差异均有统计学意义（P<0.05）；地黄饮子低剂量组GLUT3蛋白表达增加，地黄饮子中剂量组GLUT1蛋白表达增加，GSK-3β蛋白表达降低，差异均有统计学意义（P<0.05）；地黄饮子高剂量组GLUT1蛋白表达增高，差异有统计学意义（P<0.05），GLUT3蛋白表达显著增高，差异有显著统计学意义（P<0.01），GLUT4蛋白表达升高，GSK-3β蛋白表达降低，差异均有统计学意义（P<0.05）。
3.5　PCR检测结果
3.5.1　PCR法检测小鼠黑质GLUT1、GLUT3、GLUT4和GSK-3β的mRNA表达
结果如表6所示，与正常组相比，模型组小鼠黑质GLUT1、GLUT3、GLUT4 mRNA表达显著降低，差异有显著统计学意义（P<0.01），GSK-3β表达升高，差异有统计学意义（P<0.05）。与模型组相比，阳性药组GLUT3、GLUT4表达增加，差异有统计学意义（P<0.05）；地黄饮子低剂量组GLUT3、GLUT4表达显著增加，差异有显著统计学意义（P<0.01）；地黄饮子中剂量组GLUT4表达显著增加，差异有显著统计学意义（P<0.01），GLUT1、GLUT3表达增高，差异有统计学意义（P<0.05）；地黄饮子高剂量组GLUT1、GLUT3、GLUT4表达增高，GSK-3β表达降低，差异均有统计学意义（P<0.05）。
3.5.2　PCR法检测对小鼠纹状体中GLUT1、GLUT3、GLUT4和GSK-3β的mRNA表达
结果如表7所示，与正常组相比，模型组小鼠纹状体GLUT1和GLUT3 mRNA表达显著降低，差异有显著统计学意义（P<0.01），GLUT4表达降低，GSK-3β表达升高，差异均有统计学意义（P<0.05）。与模型组相比，阳性药组GLUT3、GLUT4表达显著增加，GSK-3β蛋白表达显著降低，差异均有统计学意义（P<0.05）；地黄饮子低剂量组GLUT4表达显著增加，差异有显著统计学意义（P<0.01），GLUT3表达增加，GSK-3β表达显著降低，差异均有统计学意义（P<0.05）；地黄饮子中剂量组GLUT1表达增加，差异有统计学意义（P<0.05），GLUT3、GLUT4显著增加，差异有显著统计学意义（P<0.01），GSK-3β蛋白表达降低，差异有显著统计学意义（P<0.01）；地黄饮子高剂量组GLUT1、GLUT3、GLUT4表达增高，GSK-3β表达降低，差异均有统计学意义（P<0.05）。
3.6　免疫组化检测结果
3.6.1　免疫组化法检测各组小鼠黑质中GLUT1、GLUT3、GLUT4和GSK-3β的表达
结果见表8、插页ⅩⅩⅤ图6-插页ⅩⅩⅧ图9。与正常组相比，模型组小鼠黑质GLUT1、GLUT4的表达降低，GSK-3β表达升高，差异均有统计学意义（P<0.05）。与模型组相比，地黄饮子低剂量组GLUT1表达显著增加，差异有显著统计学意义（P<0.01），GLUT4和GLUT3表达升高，GSK-3β表达降低，差异均有统计学意义（P<0.05）；地黄饮子中剂量组GLUT1、GLUT3、GLUT4表达升高，差异有统计学意义（P<0.05）；地黄饮子高剂量组GLUT1表达显著升高，差异有显著统计学意义（P<0.01）。
3.6.2　免疫组化法检测各组小鼠纹状体中GLUT1、GLUT3、GLUT4和GSK-3β的表达结果
结果见表9、插页ⅩⅩⅨ图10-插页ⅩⅩⅫ图13。与正常组相比，模型组小鼠纹状体GLUT1表达显著降低，差异有显著统计学意义（P<0.01），GLUT4表达降低，差异有统计学意义（P<0.05）。与模型组相比，阳性药组GLUT3，GSK-3β表达降低，差异均有统计学意义（P<0.05）；地黄饮子低剂量组GLUT1表达增加，GSK-3β表达降低，差异均有统计学意义（P<0.05）；地黄饮子中剂量组GLUT1、GLUT3表达显著增加，差异有显著统计学意义（P<0.01）；地黄饮子高剂量组GLUT1、GLUT3表达显著增高，差异有显著统计学意义（P<0.01）；GLUT4表达升高，GSK-3β表达降低，差异均有统计学意义（P<0.05）。
4　讨论
收起
帕金森病是一种常见的中枢神经系统疾病，它的临床表现为运动迟缓、静止性震颤、认知功能障碍等症状。葡萄糖和能量代谢的改变是PD发病的潜在危险因素[10-11]，从糖代谢异常的角度探讨PD神经退行性疾病具有重要的医疗及社会价值。脑的正常功能活动依赖从血液中不断提供的葡萄糖来维持。脑组织中几乎无葡萄糖和氧的储备，脑的代谢特点决定脑组织必须依赖于葡萄糖的摄取才能维持正常的活动。但是葡萄糖不能自由穿过血脑屏障进入神经元，需要相应的运载工具，葡萄糖转运蛋白（Glucose transporters，GLUTs）就起着运送葡萄糖进入相应组织的作用[12]。在哺乳动物大脑中，GLUT1是脑中主要的葡萄糖运载体，在脑中分布在脑的毛细血管内皮和神经胶质细胞上，其作用是把血液循环当中的葡萄糖跨血脑屏障转运至脑脊液中，使血糖通过血脑屏障进入大脑，进入脑组织和胶质细胞，其表达水平和活性不受胰岛素浓度变化的影响[13]。它对葡萄糖分子具有高亲合力，即使在低浓度葡萄糖的情况下也能有效地转运葡萄糖分子[14]。GLUT3的表达由SLC2A3基因控制，其分布广泛，包括海马CA1、CA3区和皮层神经元等组织中。在脑内，GLUT3蛋白的含量很高，主要作用是将葡萄糖从脑脊液转运至神经元和神经胶质细胞内。它是神经元特异的葡萄糖转运蛋白，且对葡萄糖的亲和力高。GLUT3基因表达与神经元功能活动密切相关[15]。GLUT4在海马依赖的学习记忆期间的神经元葡萄糖供给中发挥重要作用，在学习记忆期间向神经元提供更多的葡萄糖供给用以维持神经元结构和功能完整性[16]。它主要存在于胰岛素敏感组织，如脂肪组织、骨骼肌和心肌中[17]。此外，该分子还在大鼠小脑、海马、下丘脑等脑部组织中表达。该分子被储存在特殊的囊泡中，并具有独特性[18]。GLUT4一般情况不能转运葡萄糖，仅在胰岛素信号分子刺激下起转运作用。在学习记忆期间的神经元葡萄糖供给中发挥重要作用。与GLUT3相似，具有高度的亲和力和转运能力。GSK-3β蛋白由基因GSK3B编码，是一种广泛表达的细胞信号转导分子，在许多细胞功能和疾病过程中发挥重要作用[19]。GSK-3β蛋白可以通过抑制胰岛素受体信号转导，导致胰岛素抵抗和糖代谢紊乱。此外，GSK-3β蛋白还可以通过调节肝酶的活性，影响葡萄糖的产生和利用，从而进一步调节血糖水平。GSK-3β蛋白主要参与细胞的生长、增殖、分化、凋亡等多种生物学过程，其活性调节与神经退行性疾病、炎症性疾病、肿瘤等多种疾病的发生和发展有关[20]。GSK-3β蛋白的磷酸化状态和活性受多种信号通路的影响，如Wnt信号通路、PI3K-AKT信号通路、MAPK/ERK信号通路等。GSK-3β蛋白在药物开发中也是一个重要的靶点，已有多种GSK-3β抑制剂被研究和应用于治疗阿尔茨海默病、帕金森病、糖尿病等疾病[21]。PD患者因GLUT1缺乏导致局部丘脑和小脑代谢不足，葡萄糖通过血脑屏障的运输受到损害，导致慢性神经性血糖低下，进而产生认知障碍和不同程度的痉挛、共济失调和肌张力障碍。在PD患者的脑组织中，GLUT1、GLUT3和GLUT4的表达水平降低，葡萄糖转运率下降，进而发生神经元能量代谢障碍，最终引起神经元退化和PD症状的出现。通过增加GLUT1、GLUT3和GLUT4的表达，提高葡萄糖向神经元的转运率，可能是防止PD进展的一个重要途径。GSK-3β蛋白在帕金森病的发病机制中也扮演了重要的角色。研究表明[22]，GSK-3β蛋白可以促进α-突触核蛋白的聚集，从而导致神经元的损伤和死亡。此外，GSK-3β蛋白也可以影响线粒体功能，从而影响神经元的代谢和生存。
中医将PD归属于“颤证”范畴，颤证以头部或肢体摇动、颤抖为主要临床表现，认为其病位在脑，其涵盖范围与PD临床发病表现重合。中医药在防治PD方面具有丰富的临床经验。中医学认为脑为奇恒之腑，汇聚元神和诸髓的致密性器官，与周身髓质联系紧密，脊髓、脑髓及骨髓均通于脑。《灵枢·海论》载“脑为髓之海，其输上在于其盖，上通于脑，合称脑髓，下在风府。”风府内通脊椎，以脊髓充养，络属于脑。肾为先天之本，精之处也，精生聚而成髓，脑为髓海，肾精尤其与“人身大主-脑”关系密切[23]。大脑的功能活动与肾息息相关，肾精所化之髓通过督脉上充于脑，激发和推动大脑的功能活动。中医认为颤证是由于肾虚髓空导致脑失所用，进而脑功能发生障碍。PD肾精虚证是指帕金森病患者肾精虚的中医辨证类型。在中医理论中，肾为先天之本，主生髓。肾精的充足与否与人体的健康密切相关，影响人体的各种生理功能和代谢活动。地黄饮子为滋肾阴、补肾阳、开窍化痰之要方，现代药理学的研究证实，地黄饮子能够提高胆碱能系统活性、改善脑组织能量代谢、提高学习记忆能力、保护神经元等作用。因此，地黄饮子在防治帕金森病方面有着巨大的潜力。以糖代谢为基础的发展与未来医药学有着密切的联系。从糖代谢的角度来看，人体处于不同的生理病理状态时，糖代谢也必然存在差异。大脑是人体消耗葡萄糖最多的器官之一，大脑糖代谢异常可能会导致PD肾精虚证的发生和发展。同时，肾精亏虚也可能会影响大脑糖代谢。总体而言，糖代谢与PD肾精虚证之间存在密切关系，糖代谢异常可能导致PD肾精虚证的发生。
SAMP8快速老化小鼠以回避反应和空间学习记忆能力呈增龄性加速衰退为主要特征，并且会出现葡萄糖代谢障碍[24]。SAMP8小鼠对MPTP的敏感性随着年龄的增长而增加。注射MPTP后可表现出自发活动显著减少，多巴胺神经元数量和酪氨酸羟化酶蛋白减少等变化[25]。因此本实验选用SAMP8小鼠，采用腹腔注射MPTP损害黑质区致密部的多巴胺能神经元构建PD肾精虚证证候模型[26]。“肾虚辨证标准”带有明显的年龄依赖特征，衰老是肾虚证的内涵，即为生理性肾虚[27]，采用经典的帕金森病相关行为学实验进行评价，包括旷场实验、爬杆实验、步态分析实验，经以上方法筛选出符合PD疾病临床表现的肾精虚证模型小鼠。旷场分析实验主要反映动物对新环境的探索，实验结果表明MPTP注射导致小鼠运动总路程、潜伏期与正常组比较明显较长，表明PD肾精虚证小鼠对新环境的探索能力下降，运动功能减低。与模型组相比，地黄饮子中剂量组在总路程上差异有统计学意义。高剂量组在潜伏期上差异有统计学意义。这表明地黄饮子能够改善PD肾精虚证小鼠的探索能力和行为表现。爬杆实验是检测小鼠运动协调行为的常用方法，可评估动物运动速度和四肢协调性，为了进一步研究小鼠探索能力下降是否与肢体协调度相关，本实验中发现，小鼠在造模后爬杆时间显著延长，表明小鼠运动协调能力下降。而给药后期地黄饮子低、高剂量组的时间明显降低。这表明地黄饮子能够改善PD肾精虚证小鼠的协调能力。步态分析实验是一种评价神经系统运动行为敏感度的检测方法。其中，四肢接触面积是小鼠在行走过程中足迹面积的变化，可以反映动物行走时肢体肌力的情况。步行周期分为支撑相和推进相，支撑相指动物肢体支撑时长与步行周期的比例。在实验中，模型组小鼠的接触面积出现异常，提示其肢体推动能力下降，异常的步行周期提示动物行走整体功能出现障碍。与模型组比较，地黄饮子高剂量组小鼠潜伏期明显缩短，推进指数、支撑时相、接触面积都明显改善，这表明地黄饮子能够改善PD肾精虚证小鼠的步态表现。
为了验证帕金森病小鼠行为学改变是否与糖代谢相关，实验检测了空腹血糖值和脑内糖代谢相关蛋白含量，空腹血糖结果显示，造模前，小鼠的空腹血糖值维持在4.5～7.5 mmol/L之间。造模后，正常组小鼠空腹血糖值稳定在正常范围6～7.5 mmol/L之间，模型组、给药组血糖上升，血糖值在8～9 mmol/L之间，给药期间，模型组小鼠血糖值持续处于高血糖状态，低、中、高剂量组各组小鼠血糖水平在给药后开始有所降低，高剂量组下降趋势明显。表明地黄饮子对PD肾精虚证小鼠具有一定的降血糖作用，通过纠正糖代谢，改善机体能量代谢发挥对PD肾精虚证小鼠的治疗作用。随着PD肾精虚证小鼠空腹血糖水平的变化，其运动功能亦不断变化，提示PD血糖水平与其运动功能及其预后状况相关。其机制可能是PD肾精虚证小鼠高血糖水平引起机体组织的代谢紊乱，侵犯感觉神经、运动神经和自主神经，累及运动神经进而导致运动功能障碍，对小鼠脑神经细胞的损伤、脑内糖代谢亦可能产生影响。采用Western Blot、免疫组化法和PCR技术对脑内糖代谢相关蛋白进行定性定量检测结果显示，在PD肾精虚证小鼠的脑黑质、纹状体组织中，GLUT1、GLUT3、GLUT4蛋白表达降低，从而导致葡萄糖转运率降低，葡萄糖转运体活性低、葡萄糖摄取量不足，神经元糖代谢异常，神经元能量代谢障碍出现PD肾精虚证的相应症状。纹状体GSK-3β表达升高，与造模前差异明显，引起神经元退化。提示PD肾精虚证模型小鼠存在脑葡萄糖摄取减少，大脑对于糖代谢的反应减弱，这可能是其发生行为紊乱及神经认知障碍的原因。PD肾精虚证小鼠脑黑质GLUT1、GLUT4、GSK-3β，脑纹状体GLUT1、GLUT3、GLUT4、GSK-3β蛋白含量在给药后期均与模型组有差异；脑黑质、纹状体GLUT1、GLUT3、GLUT4、GSK-3βm RNA含量在给药后期均与模型组有差异，地黄饮子低剂量组的效果差于中、高剂量组。提示地黄饮子治疗1个月后改善了小鼠脑内葡萄糖代谢异常，表明地黄饮子可以通过调节GLUT1、GLUT3、GLUT4、GSK-3β蛋白含量、mRNA含量，提高PD肾精虚证小鼠黑质和纹状体组织中糖代谢水平，改善PD肾精虚证小鼠神经传导功能的作用。综上所述，地黄饮子可以降低血糖水平并改善小鼠的运动能力，调节帕金森病小鼠黑质、纹状体中GLUT1、GLUT3、GLUT4、GSK-3β蛋白、mRNA的表达，表明其可能通过影响糖代谢通路来改善帕金森病的症状。增加葡萄糖从血液转运至大脑从而改善神经元的能量代谢很有可能是防止PD肾精虚证进展的一个重要途径。
基金
收起
  • 国家自然科学基金项目(8187152326)
文献
收起
参考文献 引证文献
排序方式：
［1］
闫川慧，张俊龙，郭蕾，等. 颤振中医治疗方案的文献研究［J］. 辽宁中医杂志，2010，37（8）：1464-1465.
［2］
陈桑桑，李清华. 帕金森病与糖尿病相关机制研究进展［J］. 世界最新医学信息文摘，2019，19（99）：117-118.
［3］
王孟迪，魏山山，姜宁，等. 金钗石斛对MPTP诱导PD小鼠的神经保护作用及机制研究［J］. 中国比较医学杂志，2022，32（1）：48-56.
［4］
朱斌，王策，徐青青. 地黄饮子联合认知康复治疗帕金森病轻度认知障碍临床研究［J］. 新中医，2021，53（17）：38-41.
［5］
成金枝，张俊龙，郭蕾，等. 阿尔茨海默病肾虚证病证结合动物模型的制备及验证［J］. 中华中医药杂志，2018，33（3）：1063-1066.
［6］
胡雅岑，徐倩，郭纪峰，等. MPTP诱导的帕金森病小鼠模型黑质脑组织DNA甲基化研究［J］. 生物化学与生物物理进展，2015，42（3）：277-285.
［7］
李玉明，廖程娟，朱沅如，等. 白簕中性多糖对2型糖尿病小鼠糖脂代谢的作用［J］. 中国民族民间医药，2022，31（20）：12-17.
［8］
于锦锦，薛雁，刘翠，等. 苍白球大麻素对大鼠运动行为的调控及受体机制［J］. 青岛大学学报（医学版），2021，57（2）：178-181.
［9］
李艳荣，樊慧杰，柴智，等. 五子衍宗丸对帕金森病小鼠的神经保护及抗炎作用［J］. 中华中医药杂志，2020，35（7）：3623-3626.
［10］
RYU W I，BORMANN M K，SHEN M Q，et al. Brain cells derived from Alzheimer’s disease patients have multiple specific innate abnormalities in energy metabolism［J］. Mol Psychiatry，2021，26：5702-5714.
［11］
VIHAR P，THOMAS R，SHAHRIAR S，et al. Energy metabolism deficits in Alzheimer disease［J］. Modern Pathology，2019，32.
［12］
文雯，高丽娟，魏江平，等. 能量代谢与阿尔茨海默病研究进展［J］. 世界科学技术-中医药现代化，2018，20（12）：2145-2149.
［13］
DICK A P，HARIK SI，KLIP A，et al. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity［J］. Proc Natl Acad Sci USA，1984，81（22）：7233-7237.
［14］
KOCH H，WEBER Y G. The glucose transporter type1（Glut1）syndromes［J］. Epilepsy Behav，2019，91：90-93.
［15］
魏兰兰，任煦，赵妍妍，等. 易化型葡萄糖转运体的表达、分布及相关疾病的研究进展［J］. 生理学报，2019，71（2）：350-360.
［16］
衣雪洁，孙玉霞，姚婷婷，等. 急、慢性运动对2型糖尿病大鼠脂肪PI3K/AKT/GLUT4通路的影响［J］. 中国应用生理学杂志，2020，36（1）：12-16.
［17］
WANG T N，WANGJ，HU X G，et al. Current understanding of glucose transporter 4 expression and functional mechanisms［J］. World JBiol Chem，2020，11（3）：76-98.
［18］
刘佩. 益智健脑颗粒对AD模型大鼠海马胰岛素受体和葡萄糖转运蛋白4mRNA表达的影响［D］. 长沙：中南大学，2011.
［19］
MISHRA N，BASU A，JAYAPRAKASH V，et al. Structure based virtual screening of GSK-3β：importance of protein flexibility and induced fit［J］. Bioorg Med Chem Lett，2009，19（19）：5582-5585.
［20］
VALLÉE A，VALLÉE J N，LECARPENTIER Y. Potential role of cannabidiol in Parkinson’s disease by targeting the WNT/β-catenin pathway，oxidative stress and inflammation［J］. Aging（Albany NY），2021，13（7）：10796-10813.
［21］
KHAN SS，JANRAOS，SRIVASTAVA S，et al. GSK-3β：an exuberating neuroinflammatory mediator in Parkinson’s disease［J］. Biochem Pharmacol，2023，210：115496.
［22］
DEMURO S，DIMARTINOR M C，ORTEGA JA，et al. GSK-3β，FYN，and DYRK1A：master regulators in neurodegenerative pathways［J］. Int JMol Sci，2021，22（16）：9098.
［23］
杨远滨，沈沁暄. 帕金森病中医研究现状［J］. 光明中医，2018，33（20）：3104-3106.
［24］
TONG JJ，CHEN G H，WANG F，et al. Chronic acarbose treatment alleviates age-related behavioral and biochemical changes in SAMP8 mice［J］. Behav Brain Res，2015，284：138-152.
［25］
孙筱璇，薛莉，周畅，等. 晚期糖基化终末产物受体对帕金森病模型小鼠脑内酪氨酸羟化酶表达的影响［J］. 中国临床神经科学，2017，25（1）：1-7.
［26］
周丽丽，莫超然，刘心朗，等. 蒙药香青兰总黄酮对帕金森病模型小鼠的神经保护作用［J］. 中国比较医学杂志，2021，31（5）：41-46.
［27］
沈自尹，黄建华，林伟，等. 从整体论到系统生物学进行肾虚和衰老的研究［J］. 中国中西医结合杂志，2009，29（6）：548-550.
2025年第43卷第11期
PDF下载
28
12
引用本文
BibTeX
文章信息
doi: 10.13193/j.issn.1673-7717.2025.11.023
  • 首发时间：2026-10-30
  • 出版时间：2025-11-10
补充材料
相关文章
文章信息
作者
出版历史
基金
国家自然科学基金项目(8187152326)
作者信息
    山西中医药大学，山西 太原 030619

通讯作者:

赵琼（1979-），女，山西晋中人，副教授，硕士研究生导师，博士，研究方向：藏象理论。E-mail：。
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2025.11.023
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62662699（运营及技术支持）
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持