首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1315688480940871924, tenantId=1146029695717560320, journalId=1315121837170065538, issueId=1315688435411694395, articleNumber=null, orderNo=null, doi=10.16368/j.issn.1674-8999.2025.12.415, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1749398400000, receivedDateStr=2025-06-09, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1791614178165, onlineDateStr=2026-10-10, pubDate=1765296000000, pubDateStr=2025-12-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1791614178165, onlineIssueDateStr=2026-10-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1791614178165, creator=13701087609, updateTime=1791614178165, updator=13701087609, issue=Issue{id=1315688435411694395, tenantId=1146029695717560320, journalId=1315121837170065538, year='2025', volume='40', issue='12', pageStart='2487', pageEnd='2712', issueExtLink='null', onlineDate='null', pubDate='1765296000000', pubDateStr='2025-12-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1791614167309, creator='13701087609', updateTime=1791616084449, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1315696476567744680, tenantId=1146029695717560320, journalId=1315121837170065538, issueId=1315688435411694395, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1315696476571938985, tenantId=1146029695717560320, journalId=1315121837170065538, issueId=1315688435411694395, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2668, endPage=2677, ext={EN=ArticleExt(id=1315688481364496629, articleId=1315688480940871924, tenantId=1146029695717560320, journalId=1315121837170065538, language=EN, title=Action Mechanism of Zuogui Pill Inhibiting Cellular Senescence and Protecting Parkinson′s Disease Mice Based on p53/p21 Pathway, columnId=1315688455783428135, journalTitle=Acta Chinese Medicine, columnName=Experimental Study, runingTitle=null, highlight=null, articleAbstract=

Objective:To explore the neuroprotective mechanism of Zuogui Pills in Parkinson's disease（PD）mice based on the p53/p21 pathway.Methods:Sixty male C57BL/6 mice were randomly divided into a control group，model group，low-dose Zuogui Pills group（1.8 g·kg-1·d-1），medium-dose Zuogui Pills group（3.6 g·kg-1·d-1），high-dose Zuogui Pills group（7.2 g·kg-1·d-1），and Madopar group（50 mg·kg-1·d-1）using a random number table method.Except for the control group，all other groups were modeled by intraperitoneal injection with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine（MPTP）（30 mg·kg-1·d-1）for five consecutive days.From the first day of modeling，the treatment groups were administered orally once daily for 10 days. Behavioral assessment，immunohistochemistry，Western Blot，ELISA，β-galactosidase（SA-β-gal）staining，and immunofluorescence staining were used to observe the effect of Zuogui Pills on cellular senescence in PD mice.Results:The open field test results showed that，compared with the control group，the total distance traveled by mice in the model group was reduced（P＜0.01）；compared with the model group，the total distance traveled by mice in the medium-dose and high-dose Zuogui Pill groups，as well as the Madopar group，was increased（P＜0.01）.The pole-climbing test results showed that，compared with the control group，the time for mice in the model group to climb the pole was prolonged（P＜0.05）；compared with the model group，the pole -climbing time was shortened in the high-dose Zuogui Pill group（P＜0.05）.Immunohistochemistry and Western Blot detection of tyrosine hydroxylase（TH）protein showed that，compared with the control group，TH protein expression in the model group was decreased（P＜0.01）；compared with the model group，TH protein expression was increased in the medium-dose and high-dose Zuogui Pill groups，as well as in the Madopar group（P＜0.05 or P＜0.01）.ELISA results showed that，compared with the control group，the levels of dopamine（DA），dihydroxy-phenyl acetic acid（DOPAC），and homovanillic acid（HVA）in the substantia nigra and striatum tissues of the model group were decreased（P＜0.01）；compared with the model group，the levels of DA，DOPAC，and HVA in the substantia nigra and striatum tissues were increased in the low-dose，medium-dose，and high-dose Zuogui Pill groups，as well as in the Madopar group（P＜0.05 or P＜0.01）.Immunofluorescence double staining results showed that compared with the control group，the number of Lamin B1（nuclear lamina protein B1）positive cells in the model group was reduced（P＜0.01），and the number of GFAP（glial fibrillary acidic protein）positive cells was increased（P＜0.01）. Compared with the model group，the numbers of Lamin B1 positive cells in the low-dose，medium-dose，and high-dose Zuogui pills groups，as well as in the Madopar group，were increased（P＜0.01），while the numbers of GFAP positive cells were decreased（P＜0.05 or P＜0.01）.Western blot results showed that compared with the control group，the protein levels of p53（tumor protein 53，TP53），CDKN1A（Cyclin-dependent kinase inhibitor 1A，p21），and CDKN2A（Cyclin-dependent kinase inhibitor 2A，p16）in the substantia nigra tissue of the model group were all elevated（P＜0.01）. Compared with the model group，the protein levels of p53，p21，and p16 in the substantia nigra tissue were reduced in the low-dose，medium-dose，and high-dose Zuogui pills groups，as well as in the Madopar group（P＜0.01）.SA-β-gal staining results showed that compared with the control group，the area of SA-β-gal positive expression in the substantia nigra tissue of the model group was increased（P＜0.01）；compared with the model group，the area of SA-β-gal positive expression was decreased in the medium-dose and high-dose Zuogui pills groups，as well as in the Madopar group（P＜0.05 or P＜0.01）.ELISA results showed that compared with the control group，the levels of IL-6 and IL-8 in the substantia nigra tissue of the model group were increased（P＜0.01）；compared with the model group，the levels of IL-6 and IL-8 in the substantia nigra tissue were reduced in the low-，medium-，and high-dose Zuogui Pill groups，as well as in the Madopar group（P＜0.05 or P＜0.01）. Conclusion:Zuogui Pill may exert a protective effect on PD model mice by alleviating cellular senescence through inhibition of the p53/p21 pathway.

, authors=Jin XU1, Dongdong YANG2, Mao LI1, authorsList=Jin XU, Dongdong YANG, Mao LI, authorCompany=null, correspAuthors=Mao LI, 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=1315688484816408852, articleId=1315688480940871924, tenantId=1146029695717560320, journalId=1315121837170065538, language=CN, title=基于p53/p21通路探讨左归丸抑制细胞衰老保护帕金森病小鼠的作用机制, columnId=1315688455959588905, journalTitle=中医学报, columnName=实验研究, runingTitle=null, highlight=null, articleAbstract=

目的：基于p53/p21通路探讨左归丸对帕金森病（Parkinson's disease，PD）小鼠的脑保护作用机制。方法：采用随机数字表法将60只雄性C57BL/6小鼠分为对照组、模型组、左归丸低剂量组（1.8 g·kg-1·d-1）、左归丸中剂量组（3.6 g·kg-1·d-1）、左归丸高剂量组（7.2 g·kg-1·d-1）、美多芭组（50 mg·kg-1·d-1）。除对照组外，其余各组小鼠均通过腹腔注射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·d-1）建立PD模型，连续5d。从造模第1天起，各给药组同步开始灌胃给药，每日1次，持续10 d。采用行为学评估、免疫组化、Western Blot、Elisa、β-半乳糖苷酶（β-galactosidase，SA-β-gal）染色、免疫荧光染色法观察左归丸对PD小鼠细胞衰老的影响。结果：旷场实验结果显示，与对照组比较，模型组小鼠旷场运动总距离缩短（P＜0.01）；与模型组比较，左归丸中剂量组、左归丸高剂量组及美多芭组小鼠运动总距离增加（P＜0.01）。爬杆实验结果显示，与对照组比较，模型组小鼠爬杆时间延长（P＜0.05）；与模型组比较，左归丸高剂量组爬杆时间缩短（P＜0.05）。免疫组织化学染色及Western Blot法检测酪氨酸羟化酶（tyrosine hydroxylase，TH）蛋白结果显示，与对照组比较，模型组TH蛋白表达降低（P＜0.01）；与模型组比较，左归丸中剂量组、左归丸高剂量组及美多芭组TH蛋白表达升高（P＜0.05或P＜0.01）。Elisa结果显示，与对照组比较，模型组黑质组织和纹状体组织多巴胺（dopamine，DA）、二羟基苯基乙酸（dihydroxy -phenyl acetic acid，DOPAC）、高香草酸（homovanillic acid，HVA）水平降低（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织和纹状体组织DA、DOPAC、HVA水平均升高（P＜0.05或P＜0.01）。免疫荧光双染检测结果显示，与对照组比较，模型组核纤层蛋白B1（nuclear lamina protein B1，Lamin B1）阳性细胞数减少（P＜0.01），胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）阳性细胞数增加（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组Lamin B1阳性细胞数增加（P＜0.05或P＜0.01），GFAP阳性细胞数减少（P＜0.01）。Western blot检测结果显示，与对照组比较，模型组黑质组织p53（tumour protein 53，TP53）、细胞周期蛋白依赖性激酶抑制剂1A（Cyclin-dependent kinase inhibitor 1A，CDKN1A，p21）、细胞周期蛋白依赖性激酶抑制剂2A（Cyclin-dependent kinase inhibitor 2A，CDKN2A，p16）蛋白表达均升高（P＜0.01）；与模型组相比，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织p53、p21、p16蛋白表达均降低（P＜0.01）。SA-β-gal染色法结果显示，与对照组比较，模型组黑质组织SA-β-gal蛋白阳性表达面积增加（P＜0.01）；与模型组相比，左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织SA-β-gal蛋白阳性表达面积降低（P＜0.05或P＜0.01）。Elisa检测结果显示，与对照组比较，模型组黑质组织IL-6、IL-8水平均升高（P＜0.01）；与模型组相比，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织IL-6、IL-8水平均降低（P＜0.05或P＜0.01）。结论：左归丸可能通过抑制p53/p21通路，减轻细胞衰老，从而对PD模型小鼠发挥保护作用。

, authors=徐进1, 杨东东2, 李毛1, authorsList=徐进, 杨东东, 李毛, authorCompany=null, correspAuthors=李毛, authorNote=

徐进（1980 -），男，河南驻马店人，医学硕士，副主任医师，研究方向：中医药防治帕金森病。

, correspAuthorsNote=
李毛（1986 -），男，河南驻马店人，医学博士，研究方向：中医药防治帕金森病。E -mail:
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=3GSDF8ZDBwzrO/LYP+c18g==, magXml=WVHRmaStmitTiQsDvRNRbQ==, pdfUrl=null, pdf=DQbmlubgXdQ7OTeeAO4Exg==, pdfFileSize=3815249, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=2oXW5kF8vC53Z/HGxg7Bdg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=pjmxvdXihkmzkCCa1qqeUA==, mapNumber=null, fund=null)}, authors=[Author(id=1315688485256810780, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, 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=1315688485344891166, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485256810780, language=EN, stringName=Jin XU, firstName=Jin, middleName=null, lastName=XU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1315688485424582943, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485256810780, language=CN, stringName=徐进, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1河南中医药大学第一附属医院，河南 郑州 450000, bio={"content":"

徐进（1980 -），男，河南驻马店人，医学硕士，副主任医师，研究方向：中医药防治帕金森病。

"}, bioImg=null, bioContent=

徐进（1980 -），男，河南驻马店人，医学硕士，副主任医师，研究方向：中医药防治帕金森病。

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1315688485084844309, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=1, ext=[AuthorCompanyExt(id=1315688485093232918, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000), AuthorCompanyExt(id=1315688485105815831, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1河南中医药大学第一附属医院，河南 郑州 450000)])]), Author(id=1315688485483303201, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, 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=1315688485558800675, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485483303201, language=EN, stringName=Dongdong YANG, firstName=Dongdong, middleName=null, lastName=YANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2The Affiliated Hospital to Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan China 610075, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1315688485625909540, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485483303201, language=CN, stringName=杨东东, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2成都中医药大学附属医院，四川 成都 610075, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1315688485177119000, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=2, ext=[AuthorCompanyExt(id=1315688485189701913, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485177119000, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2The Affiliated Hospital to Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan China 610075), AuthorCompanyExt(id=1315688485193896218, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485177119000, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2成都中医药大学附属医院，四川 成都 610075)])]), Author(id=1315688485697212710, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=1378172347@qq.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1315688485772710184, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485697212710, language=EN, stringName=Mao LI, firstName=Mao, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1315688485844013353, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485697212710, language=CN, stringName=李毛, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1河南中医药大学第一附属医院，河南 郑州 450000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1315688485084844309, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=1, ext=[AuthorCompanyExt(id=1315688485093232918, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000), AuthorCompanyExt(id=1315688485105815831, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1河南中医药大学第一附属医院，河南 郑州 450000)])])], keywords=[Keyword(id=1315688485965648170, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, orderNo=1, keyword=Zuogui Pill), Keyword(id=1315688486028562731, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, orderNo=2, keyword=cellular senescence), Keyword(id=1315688486112448812, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, orderNo=3, keyword=Parkinson's disease), Keyword(id=1315688486187946285, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, orderNo=4, keyword=p53/p21 pathway), Keyword(id=1315688486309581102, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, orderNo=1, keyword=左归丸), Keyword(id=1315688486393467183, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, orderNo=2, keyword=细胞衰老), Keyword(id=1315688486452187440, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, orderNo=3, keyword=帕金森病), Keyword(id=1315688486510907697, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, orderNo=4, keyword=p53/p21通路)], refs=[Reference(id=1315688488704528716, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=403, issue=10423, pageStart=293, pageEnd=304, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=MORRIS H R, SPILLANTINI M G, SUE C M, journalName=Lancet, refType=null, unstructuredReference=MORRIS H R, SPILLANTINI M G, SUE C M, et al. The pathogenesis of Parkinson's disease[J]. Lancet, 2024, 403(10423):293-304., articleTitle=The pathogenesis of Parkinson's disease, refAbstract=null), Reference(id=1315688488784220493, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=391, issue=5, pageStart=442, pageEnd=452, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=TANNER C M, OSTREM J L, journalName=N Engl J Med, refType=null, unstructuredReference=TANNER C M, OSTREM J L. Parkinson's Disease[J]. N Engl J Med, 2024, 391(5):442-452., articleTitle=Parkinson's Disease, refAbstract=null), Reference(id=1315688488910049614, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2018, volume=33, issue=1, pageStart=156, pageEnd=159, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=ROSSI A, BERGER K, CHEN H, journalName=Mov Disord, refType=null, unstructuredReference=ROSSI A, BERGER K, CHEN H, et al. Projection of the prevalence of Parkinson's disease in the coming decades:Revisited[J]. Mov Disord, 2018, 33(1):156-159., articleTitle=Projection of the prevalence of Parkinson's disease in the coming decades:Revisited, refAbstract=null), Reference(id=1315688488985547087, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=37, issue=6, pageStart=75, pageEnd=82, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=徐进, 张怀亮, 杨东东, journalName=中医研究, refType=null, unstructuredReference=徐进,张怀亮,杨东东, 等. 莫诺苷抑制铁死亡保护MPP +诱导的PC12细胞模型的机制研究[J]. 中医研究, 2024, 37(6):75-82., articleTitle=莫诺苷抑制铁死亡保护MPP +诱导的PC12细胞模型的机制研究, refAbstract=null), Reference(id=1315688489262371152, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2023, volume=30, issue=10, pageStart=2280, pageEnd=2292, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=JIANG S Y, TIAN T, YAO H, journalName=Cell Death Differ, refType=null, unstructuredReference=JIANG S Y, TIAN T, YAO H, et al. The cGAS-STING-YY1 axis accelerates progression of neurodegeneration in a mouse model of Parkinson's disease via LCN2-dependent astrocyte senescence[J]. Cell Death Differ, 2023, 30(10):2280-2292., articleTitle=The cGAS-STING-YY1 axis accelerates progression of neurodegeneration in a mouse model of Parkinson's disease via LCN2-dependent astrocyte senescence, refAbstract=null), Reference(id=1315688489363034449, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=45, issue=2, pageStart=268, pageEnd=281, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=SHEN Q Q, JV X H, MA X Z, journalName=Acta Pharmacol Sin, refType=null, unstructuredReference=SHEN Q Q, JV X H, MA X Z, et al. Cell senescence induced by toxic interaction between α-synuclein and iron precedes nigral dopaminergic neuron loss in a mouse model of Parkinson's disease[J]. Acta Pharmacol Sin, 2024, 45(2):268-281., articleTitle=Cell senescence induced by toxic interaction between α-synuclein and iron precedes nigral dopaminergic neuron loss in a mouse model of Parkinson's disease, refAbstract=null), Reference(id=1315688489451114834, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2021, volume=36, issue=13, pageStart=2204, pageEnd=2206, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=苏文理, 张丽梅, 纪家镛, journalName=光明中医, refType=null, unstructuredReference=苏文理,张丽梅,纪家镛, 等. 左归丸加减治疗肝肾阴虚型帕金森病临床观察[J]. 光明中医, 2021, 36(13):2204-2206., articleTitle=左归丸加减治疗肝肾阴虚型帕金森病临床观察, refAbstract=null), Reference(id=1315688489518223699, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2018, volume=40, issue=1, pageStart=181, pageEnd=183, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=姚建平, 李琳, 牛巧能, journalName=,中成药, refType=null, unstructuredReference=姚建平,李琳,牛巧能, 等. 左归丸对自然衰老大鼠海马乙酰胆碱含量及学习记忆功能的影响[J],中成药, 2018, 40(1):181-183., articleTitle=左归丸对自然衰老大鼠海马乙酰胆碱含量及学习记忆功能的影响, refAbstract=null), Reference(id=1315688489581138260, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2020, volume=91, issue=8, pageStart=795, pageEnd=808, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=JANKOVIC J, TAN E K, journalName=J Neurol Neurosurg Psychiatry, refType=null, unstructuredReference=JANKOVIC J, TAN E K. Parkinson's disease:etiopathogenesis and treatment[J]. J Neurol Neurosurg Psychiatry, 2020, 91(8):795-808., articleTitle=Parkinson's disease:etiopathogenesis and treatment, refAbstract=null), Reference(id=1315688489644052821, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2025, volume=47, issue=4, pageStart=1297, pageEnd=1304, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=李毛, 兰瑞, 杨东东, journalName=中成药, refType=null, unstructuredReference=李毛,兰瑞,杨东东, 等. 莫诺苷通过Nrf2/ARE通路抑制铁死亡对帕金森病小鼠的保护作用[J]. 中成药, 2025, 47(4):1297-1304., articleTitle=莫诺苷通过Nrf2/ARE通路抑制铁死亡对帕金森病小鼠的保护作用, refAbstract=null), Reference(id=1315688489719550294, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2023, volume=23, issue=1, pageStart=218, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=LI M, ZHANG J, JIANG L, journalName=BMC Complement Med Ther, refType=null, unstructuredReference=LI M, ZHANG J, JIANG L, et al. Neuroprotective effects of morroniside from Cornus officinalis sieb.Et zucc against Parkinson's disease via inhibiting oxidative stress and ferroptosis[J]. BMC Complement Med Ther, 2023, 23(1):218., articleTitle=Neuroprotective effects of morroniside from Cornus officinalis sieb.Et zucc against Parkinson's disease via inhibiting oxidative stress and ferroptosis, refAbstract=null), Reference(id=1315688489782464855, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2017, volume=39, issue=2, pageStart=260, pageEnd=265, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=佟雷, 刘金丽, 孙琳林, journalName=中成药, refType=null, unstructuredReference=佟雷,刘金丽,孙琳林, 等. 左归丸及右归丸对卵巢早衰小鼠卵巢衰老的预防作用[J]. 中成药, 2017, 39(2):260-265., articleTitle=左归丸及右归丸对卵巢早衰小鼠卵巢衰老的预防作用, refAbstract=null), Reference(id=1315688489845379416, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2019, volume=56, issue=4, pageStart=2728, pageEnd=2740, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=SALVATORE M F, MCINNIS T R, CANTU M A, journalName=Mol Neurobiol, refType=null, unstructuredReference=SALVATORE M F, MCINNIS T R, CANTU M A, et al. Tyrosine Hydroxylase Inhibition in Substantia Nigra Decreases Movement Frequency[J]. Mol Neurobiol, 2019, 56(4):2728-2740., articleTitle=Tyrosine Hydroxylase Inhibition in Substantia Nigra Decreases Movement Frequency, refAbstract=null), Reference(id=1315688489912488281, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=29, issue=18, pageStart=4318, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=LORENC-KOCI E, KAMI? SKA K, LENDA T, journalName=Molecules, refType=null, unstructuredReference=LORENC-KOCI E, KAMI? SKA K, LENDA T, et al. The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5),Sildenafil,in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats[J]. Molecules, 2024, 29(18):4318., articleTitle=The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5),Sildenafil,in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats, refAbstract=null), Reference(id=1315688489987985754, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2023, volume=48, issue=4, pageStart=1222, pageEnd=1232, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=FORREST S L, KIM J H, CROCKFORD D R, journalName=Neurochem Res, refType=null, unstructuredReference=FORREST S L, KIM J H, CROCKFORD D R, et al. Distribution Patterns of Astrocyte Populations in the Human Cortex[J]. Neurochem Res, 2023, 48(4):1222-1232., articleTitle=Distribution Patterns of Astrocyte Populations in the Human Cortex, refAbstract=null), Reference(id=1315688490063483227, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=22, issue=3, pageStart=129, pageEnd=135, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=YAN X, ZENG R, CAO Y, journalName=J Appl Biomed, refType=null, unstructuredReference=YAN X, ZENG R, CAO Y. Astragaloside IV confronts amyloid-beta-induced astrocyte senescence via hsp90aa1[J]. J Appl Biomed, 2024, 22(3):129-135., articleTitle=Astragaloside IV confronts amyloid-beta-induced astrocyte senescence via hsp90aa1, refAbstract=null), Reference(id=1315688490126397788, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=147, issue=1, pageStart=78, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=FANCY N N, SMITH A M, CARAMELLO A, journalName=Acta Neuropathol, refType=null, unstructuredReference=FANCY N N, SMITH A M, CARAMELLO A, et al. Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics[J]. Acta Neuropathol, 2024, 147(1):78., articleTitle=Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics, refAbstract=null), Reference(id=1315688490189312349, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2023, volume=24, issue=1, pageStart=23, pageEnd=39, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=BRANDEBURA A N, PAUMIER A, ONUR T S, journalName=Nat Rev Neurosci, refType=null, unstructuredReference=BRANDEBURA A N, PAUMIER A, ONUR T S, et al. Astrocyte contribution to dysfunction,risk and progression in neurodegenerative disorders[J]. Nat Rev Neurosci, 2023, 24(1):23-39., articleTitle=Astrocyte contribution to dysfunction,risk and progression in neurodegenerative disorders, refAbstract=null), Reference(id=1315688490273198430, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2025, volume=S0006-3223, issue=25, pageStart=01125, pageEnd=4, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=BADIA-SOTERAS A, MAK A, BLOK T M, journalName=Biol Psychiatry, refType=null, unstructuredReference=BADIA-SOTERAS A, MAK A, BLOK T M, et al. Astrocyte-synapse structural plasticity in neurodegenerative and neuropsychiatric diseases[J]. Biol Psychiatry, 2025, S0006-3223(25):01125-4., articleTitle=Astrocyte-synapse structural plasticity in neurodegenerative and neuropsychiatric diseases, refAbstract=null), Reference(id=1315688490336112991, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=21, issue=1, pageStart=81, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=WANG M, TIAN T, ZHOU H, journalName=J Neuroinflammation, refType=null, unstructuredReference=WANG M, TIAN T, ZHOU H, et al. Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling[J]. J Neuroinflammation, 2024, 21(1):81., articleTitle=Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling, refAbstract=null), Reference(id=1315688490403221856, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2022, volume=21, issue=1, pageStart=e13521, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=MATIAS I, DINIZ L P, DAMICO I V, journalName=Aging Cell, refType=null, unstructuredReference=MATIAS I, DINIZ L P, DAMICO I V, et al. Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus[J]. Aging Cell, 2022, 21(1):e13521., articleTitle=Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus, refAbstract=null), Reference(id=1315688490474525025, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2022, volume=4, issue=8, pageStart=995, pageEnd=1006, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=JEON O H, MEHDIPOUR M, GIL T H, journalName=Nat Metab, refType=null, unstructuredReference=JEON O H, MEHDIPOUR M, GIL T H, et al. Systemic induction of senescence in young mice after single heterochronic blood exchange[J]. Nat Metab, 2022, 4(8):995-1006., articleTitle=Systemic induction of senescence in young mice after single heterochronic blood exchange, refAbstract=null), Reference(id=1315688490545828194, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=25, issue=12, pageStart=958, pageEnd=978, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=WANG B, HAN J, ELISSEEFF J H, journalName=Nat Rev Mol Cell Biol, refType=null, unstructuredReference=WANG B, HAN J, ELISSEEFF J H, et al. The senescence-associated secretory phenotype and its physiological and pathological implications[J]. Nat Rev Mol Cell Biol, 2024, 25(12):958-978., articleTitle=The senescence-associated secretory phenotype and its physiological and pathological implications, refAbstract=null), Reference(id=1315688490633908579, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2024, volume=25, issue=13, pageStart=7411, pageEnd=null, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=LAWRENCE M, GOYAL A, PATHAK S, journalName=Int J Mol Sci, refType=null, unstructuredReference=LAWRENCE M, GOYAL A, PATHAK S, et al. Cellular Senescence and Inflammaging in the Bone:Pathways,Genetics,Anti-Aging Strategies and Interventions[J]. Int J Mol Sci, 2024, 25(13):7411., articleTitle=Cellular Senescence and Inflammaging in the Bone:Pathways,Genetics,Anti-Aging Strategies and Interventions, refAbstract=null), Reference(id=1315688490701017444, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2019, volume=25, issue=4, pageStart=514, pageEnd=530.e8, url=null, language=null, rfNumber=[25], rfOrder=24, authorNames=RIESSLAND M, KOLISNYK B, KIM T W, journalName=Cell Stem Cell, refType=null, unstructuredReference=RIESSLAND M, KOLISNYK B, KIM T W, et al. Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons[J]. Cell Stem Cell, 2019, 25(4):514-530.e8., articleTitle=Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons, refAbstract=null), Reference(id=1315688490776514917, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2018, volume=15, issue=1, pageStart=166, pageEnd=null, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=WILLIAMS-GRAY C H, WIJEYEKOON R S, SCOTT K M, journalName=J Neuroinflammation, refType=null, unstructuredReference=WILLIAMS-GRAY C H, WIJEYEKOON R S, SCOTT K M, et al. Abnormalities of age-related T cell senescence in Parkinson's disease[J]. J Neuroinflammation, 2018, 15(1):166., articleTitle=Abnormalities of age-related T cell senescence in Parkinson's disease, refAbstract=null), Reference(id=1315688490839429478, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2021, volume=10, issue=7, pageStart=1694, pageEnd=null, url=null, language=null, rfNumber=[27], rfOrder=26, authorNames=VERMA D K, SEO B A, GHOSH A, journalName=Cells, refType=null, unstructuredReference=VERMA D K, SEO B A, GHOSH A, et al. Alpha-Synuclein Preformed Fibrils Induce Cellular Senescence in Parkinson's Disease Models[J]. Cells, 2021, 10(7):1694., articleTitle=Alpha-Synuclein Preformed Fibrils Induce Cellular Senescence in Parkinson's Disease Models, refAbstract=null), Reference(id=1315688490906538343, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, doi=null, pmid=null, pmcid=null, year=2023, volume=12, issue=2, pageStart=444, pageEnd=null, url=null, language=null, rfNumber=[28], rfOrder=27, authorNames=BULBIANKOVA D, DIAZ-PUERTAS R, ALVAREZ-MARTINEZ F J, journalName=Antioxidants (Basel), refType=null, unstructuredReference=BULBIANKOVA D, DIAZ-PUERTAS R, ALVAREZ-MARTINEZ F J, et al. Hallmarks and Biomarkers of Skin Senescence:An Updated Review of Skin Senotherapeutics[J]. Antioxidants (Basel), 2023, 12(2):444., articleTitle=Hallmarks and Biomarkers of Skin Senescence:An Updated Review of Skin Senotherapeutics, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1315688485084844309, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=1, ext=[AuthorCompanyExt(id=1315688485093232918, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000), AuthorCompanyExt(id=1315688485105815831, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1河南中医药大学第一附属医院，河南 郑州 450000)]), AuthorCompany(id=1315688485177119000, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=2, ext=[AuthorCompanyExt(id=1315688485189701913, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485177119000, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2The Affiliated Hospital to Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan China 610075), AuthorCompanyExt(id=1315688485193896218, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485177119000, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2成都中医药大学附属医院，四川 成都 610075)])], figs=[ArticleFig(id=1315688486640931122, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=IuKppvtIunQVjxHvcuufIA==, figureFileBig=2oXW5kF8vC53Z/HGxg7Bdg==, tableContent=null), ArticleFig(id=1315688486703845683, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=图1, caption=左归丸对PD小鼠旷场实验的影响

注：A：对照组；B：模型组；C：左归丸低剂量组；D：左归丸中剂量组；E：左归丸高剂量组；F：美多芭组。

, figureFileSmall=IuKppvtIunQVjxHvcuufIA==, figureFileBig=2oXW5kF8vC53Z/HGxg7Bdg==, tableContent=null), ArticleFig(id=1315688486913560884, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=XBU9qFKhK3/7+bFagYxtOQ==, figureFileBig=HCwt2/Xkh8m3FN/AnjwHfQ==, tableContent=null), ArticleFig(id=1315688486993252661, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=图2, caption=左归丸对黑质、纹状体TH蛋白表达的影响

注：（a）TH免疫组织化学染色（×400）；（b）Western blot检测TH蛋白。A：对照组；B：模型组；C：左归丸低剂量组；D：左归丸中剂量组；E：左归丸高剂量组；F：美多芭组。

, figureFileSmall=XBU9qFKhK3/7+bFagYxtOQ==, figureFileBig=HCwt2/Xkh8m3FN/AnjwHfQ==, tableContent=null), ArticleFig(id=1315688487060361526, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=fnrzucK6CjFGcdCutap5lA==, figureFileBig=agD3AQ0hQSPIi9JL6CKn8A==, tableContent=null), ArticleFig(id=1315688487127470391, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=图3, caption=左归丸对黑质组织Lamin B1、GFAP阳性细胞数的影响（免疫荧光双染，×400）

注：A：对照组；B：模型组；C：左归丸低剂量组；D：左归丸中剂量组；E：左归丸高剂量组；F：美多芭组。

, figureFileSmall=fnrzucK6CjFGcdCutap5lA==, figureFileBig=agD3AQ0hQSPIi9JL6CKn8A==, tableContent=null), ArticleFig(id=1315688487198773560, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=XXm24pAxm/BXWH10osk84w==, figureFileBig=bK4GchVKvRjrv3mQRx5ORA==, tableContent=null), ArticleFig(id=1315688487274271033, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=图4, caption=左归丸对p53、p21、p16蛋白表达的影响

注：A：对照组；B：模型组；C：左归丸低剂量组；D：左归丸中剂量组；E：左归丸高剂量组；F：美多芭组。

, figureFileSmall=XXm24pAxm/BXWH10osk84w==, figureFileBig=bK4GchVKvRjrv3mQRx5ORA==, tableContent=null), ArticleFig(id=1315688487341379898, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=KGG1o9puWe1p/Fsjj3UQ8g==, figureFileBig=4gKOMuv0WAAVz+jp8tTs0g==, tableContent=null), ArticleFig(id=1315688487412683067, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=图5, caption=左归丸对SA-β-gal蛋白表达的影响（SA-β-gal染色法，×200）

注：A：对照组；B：模型组；C：左归丸低剂量组；D：左归丸中剂量组；E：左归丸高剂量组；F：美多芭组。

, figureFileSmall=KGG1o9puWe1p/Fsjj3UQ8g==, figureFileBig=4gKOMuv0WAAVz+jp8tTs0g==, tableContent=null), ArticleFig(id=1315688487488180540, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别n旷场运动距离（s/m）爬杆时间（t/s）
对照组622.53 ±1.346.91 ±0.47
模型组64.10 ±0.46**3.41 ±0.53*
左归丸低剂量组64.93 ±0.455.07 ±0.38
左归丸中剂量组8.67 ±1.01##6.58 ±2.08
左归丸高剂量组6613.80 ±0.66##7.04 ±1.64#
美多芭组614.53 ±1.43##6.22 ±0.87
F值152.8004.193
P值＜0.0010.019
), ArticleFig(id=1315688487580455229, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表1, caption=

左归丸对PD小鼠行为学的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别n旷场运动距离（s/m）爬杆时间（t/s）
对照组622.53 ±1.346.91 ±0.47
模型组64.10 ±0.46**3.41 ±0.53*
左归丸低剂量组64.93 ±0.455.07 ±0.38
左归丸中剂量组8.67 ±1.01##6.58 ±2.08
左归丸高剂量组6613.80 ±0.66##7.04 ±1.64#
美多芭组614.53 ±1.43##6.22 ±0.87
F值152.8004.193
P值＜0.0010.019
), ArticleFig(id=1315688487660147006, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别n黑质免疫组化黑质纹状体
对照组60.37 ±0.021.00 ±0.011.00 ±0.14
模型组60.13 ±0.03**0.22 ±0.03**0.19 ±0.06**
左归丸低剂量组60.21 ±0.04##0.29 ±0.010.27 ±0.05
左归丸中剂量组60.27 ±0.01##0.44 ±0.09##0.38 ±0.06#
左归丸高剂量组60.32 ±0.03##0.78 ±0.11##0.70 ±0.09##
美多芭组60.28 ±0.02##0.61 ±0.09##0.49 ±0.12##
F值36.61039.77030.41
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688487723061567, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表2, caption=

左归丸对黑质、纹状体TH蛋白表达的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别n黑质免疫组化黑质纹状体
对照组60.37 ±0.021.00 ±0.011.00 ±0.14
模型组60.13 ±0.03**0.22 ±0.03**0.19 ±0.06**
左归丸低剂量组60.21 ±0.04##0.29 ±0.010.27 ±0.05
左归丸中剂量组60.27 ±0.01##0.44 ±0.09##0.38 ±0.06#
左归丸高剂量组60.32 ±0.03##0.78 ±0.11##0.70 ±0.09##
美多芭组60.28 ±0.02##0.61 ±0.09##0.49 ±0.12##
F值36.61039.77030.41
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688487798559040, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nDA（ρ/ng·L-1）DOPAC（ρ/μg·L-1）HVA（ρ/μg·L-1）
对照组612.26 ±1.733.90 ±0.2413.24 ±1.17
模型组66.14 ±1.35**2.16 ±0.19**5.19 ±1.18**
左归丸低剂量组68.52 ±1.31#2.57 ±0.29#7.31 ±1.39#
左归丸中剂量组69.36 ±2.09##2.86 ±0.31##8.56 ±1.42##
左归丸高剂量组611.26 ±1.86##3.43 ±0.31##11.26 ±1.24##
美多芭组610.54 ±1.84##3.30 ±0.31##10.49 ±1.81##
F值9.68230.31025.370
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688487865667905, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表3, caption=

左归丸对黑质组织DA、DOPAC、HVA水平的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nDA（ρ/ng·L-1）DOPAC（ρ/μg·L-1）HVA（ρ/μg·L-1）
对照组612.26 ±1.733.90 ±0.2413.24 ±1.17
模型组66.14 ±1.35**2.16 ±0.19**5.19 ±1.18**
左归丸低剂量组68.52 ±1.31#2.57 ±0.29#7.31 ±1.39#
左归丸中剂量组69.36 ±2.09##2.86 ±0.31##8.56 ±1.42##
左归丸高剂量组611.26 ±1.86##3.43 ±0.31##11.26 ±1.24##
美多芭组610.54 ±1.84##3.30 ±0.31##10.49 ±1.81##
F值9.68230.31025.370
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688487941165378, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nDA（ρ/ng·L-1）DOPAC（ρ/μg·L-1）HVA（ρ/μg·L-1）
对照组615.05 ±1.504.32 ±0.3714.52 ±1.16
模型组68.73 ±1.17**2.42 ±0.23**6.58 ±1.16**
左归丸低剂量组610.80 ±1.99#2.86 ±0.32#8.37 ±1.19#
左归丸中剂量组612.14 ±1.87##3.23 ±0.23##9.70 ±1.01##
左归丸高剂量组614.50 ±1.96##3.90 ±0.31##12.75 ±1.39##
美多芭组613.43 ±1.62##3.53 ±0.28##11.58 ±1.38##
F值11.72033.53043.590
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688488016662851, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表4, caption=

左归丸对纹状体组织DA、DOPAC、HVA水平的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nDA（ρ/ng·L-1）DOPAC（ρ/μg·L-1）HVA（ρ/μg·L-1）
对照组615.05 ±1.504.32 ±0.3714.52 ±1.16
模型组68.73 ±1.17**2.42 ±0.23**6.58 ±1.16**
左归丸低剂量组610.80 ±1.99#2.86 ±0.32#8.37 ±1.19#
左归丸中剂量组612.14 ±1.87##3.23 ±0.23##9.70 ±1.01##
左归丸高剂量组614.50 ±1.96##3.90 ±0.31##12.75 ±1.39##
美多芭组613.43 ±1.62##3.53 ±0.28##11.58 ±1.38##
F值11.72033.53043.590
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688488113131844, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nLamin B1GFAP
对照组6126.00 ±15.103.33 ±0.58
模型组63.33 ±3.51**40.00 ±2.00**
左归丸低剂量组618.00 ±2.00#30.33 ±2.08##
左归丸中剂量组651.67 ±8.50##14.67 ±2.52##
左归丸高剂量组673.00 ±7.55##8.33 ±0.58##
美多芭组632.67 ±3.21##21.67 ±4.04##
F值91.930108.200
P值＜0.001＜0.001
), ArticleFig(id=1315688488176046405, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表5, caption=

左归丸对黑质组织Lamin B1、GFAP阳性细胞数的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nLamin B1GFAP
对照组6126.00 ±15.103.33 ±0.58
模型组63.33 ±3.51**40.00 ±2.00**
左归丸低剂量组618.00 ±2.00#30.33 ±2.08##
左归丸中剂量组651.67 ±8.50##14.67 ±2.52##
左归丸高剂量组673.00 ±7.55##8.33 ±0.58##
美多芭组632.67 ±3.21##21.67 ±4.04##
F值91.930108.200
P值＜0.001＜0.001
), ArticleFig(id=1315688488251543878, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别np53p21p16
对照组61.00 ±0.131.01 ±0.321.01 ±0.19
模型组67.87 ±0.74**4.41 ±0.44**4.99 ±0.74**
左归丸低剂量组64.91 ±0.61##3.48 ±0.35##3.63 ±0.65##
左归丸中剂量组62.52 ±0.27##2.23 ±0.08##2.04 ±0.30##
左归丸高剂量组61.79 ±0.10##1.77 ±0.21##1.52 ±0.19##
美多芭组63.16 ±0.35##2.82 ±0.21##2.69 ±0.60##
F值99.94152.02126.035
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688488327041351, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表6, caption=

左归丸对p53、p21、p16蛋白表达的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别np53p21p16
对照组61.00 ±0.131.01 ±0.321.01 ±0.19
模型组67.87 ±0.74**4.41 ±0.44**4.99 ±0.74**
左归丸低剂量组64.91 ±0.61##3.48 ±0.35##3.63 ±0.65##
左归丸中剂量组62.52 ±0.27##2.23 ±0.08##2.04 ±0.30##
左归丸高剂量组61.79 ±0.10##1.77 ±0.21##1.52 ±0.19##
美多芭组63.16 ±0.35##2.82 ±0.21##2.69 ±0.60##
F值99.94152.02126.035
P值＜0.001＜0.001＜0.001
), ArticleFig(id=1315688488389955912, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别n阳性表达面积占比
对照组60.099 ±0.031
模型组60.576 ±0.076**
左归丸低剂量组60.514 ±0.079
左归丸中剂量组60.351 ±0.068##
左归丸高剂量组60.192 ±0.044##
美多芭组60.357 ±0.066#
F值24.97
P值＜0.001
), ArticleFig(id=1315688488461259081, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表7, caption=

左归丸对黑质SA-β-gal蛋白表达的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别n阳性表达面积占比
对照组60.099 ±0.031
模型组60.576 ±0.076**
左归丸低剂量组60.514 ±0.079
左归丸中剂量组60.351 ±0.068##
左归丸高剂量组60.192 ±0.044##
美多芭组60.357 ±0.066#
F值24.97
P值＜0.001
), ArticleFig(id=1315688488524173642, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nIL-6IL-8
对照组63.75 ±1.476.79 ±1.37
模型组69.26 ±1.31**11.40 ±1.21**
左归丸低剂量组66.68 ±1.194#9.10 ±1.10#
左归丸中剂量组65.33 ±1.56##6.92 ±0.66##
左归丸高剂量组64.82 ±1.45##6.21 ±1.61##
美多芭组66.16 ±1.38#8.45 ±1.26#
F值5.5797.341
P值0.0070.002
), ArticleFig(id=1315688488591282507, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, language=CN, label=表8, caption=

左归丸对黑质组织IL-6、IL-8水平的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nIL-6IL-8
对照组63.75 ±1.476.79 ±1.37
模型组69.26 ±1.31**11.40 ±1.21**
左归丸低剂量组66.68 ±1.194#9.10 ±1.10#
左归丸中剂量组65.33 ±1.56##6.92 ±0.66##
左归丸高剂量组64.82 ±1.45##6.21 ±1.61##
美多芭组66.16 ±1.38#8.45 ±1.26#
F值5.5797.341
P值0.0070.002
)], attaches=null, journal=Journal(id=1315120739373908093, delFlag=0, nameCn=中医学报, nameEn=Acta Chinese Medicine, nameHistory1=null, nameHistory2=null, issn=1674-8999, eissn=null, cn=41-1411/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=8b94oSAFH8bu+kilqGRUOQ==, journalPrice=null, startedYear=null, abbrevIsoEn=Acta Chinese Medicine, journalRemark=null, publicationField=null, createdTime=1791478818030, updatedTime=1791479792022, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=Z, firstLetterEn=Z, subjectCode=Medical and Pharmaceutical Sciences, subjectName=null, subjectCodeEn=Medical and Pharmaceutical Sciences, subjectNameEn=null, picCn=8b94oSAFH8bu+kilqGRUOQ==, picEn=Y56h/oCYJegF4hgM5ASRZw==, jcr=null, cjcr=null, exts=[JournalExt(id=1315124824696017555, language=CN, name=中医学报, 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=1791479792045, updatedTime=1791479792045, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://hnzyydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn/auth/realms/journal/protocol/openid-connect/auth?client_id=journal-portal&redirect_uri=https%3A%2F%2Fjournal.portal.founderss.cn%2Foauth%2Fcallback&response_type=code&scope=phone+openid+email+profile&state=6c31f9e3-672c-4715-b, submissionReviewUrl=https://hnzyydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1315124824763126420, language=EN, name=Acta 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=1791479792061, updatedTime=1791479792061, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://hnzyydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn/auth/realms/journal/protocol/openid-connect/auth?client_id=journal-portal&redirect_uri=https%3A%2F%2Fjournal.portal.founderss.cn%2Foauth%2Fcallback&response_type=code&scope=phone+openid+email+profile&state=6c31f9e3-672c-4715-b, submissionReviewUrl=https://hnzyydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1315121837170065538, websiteList=[Website(id=1315346106557518446, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1315121837170065538, 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/zyxb/CN, language=CN, createTime=1791532549752, createBy=18614031015, updateTime=1791532766964, updateBy=18614031015, name=中医学报-中文, tplId=1146099689490845704, title=中医学报, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1315347175865963357, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=articleTextType, value=kx, createTime=1791532804695, updateTime=1791532804695, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175811437402, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=banner, value=null, createTime=1791532804682, updateTime=1791532804682, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175916295008, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=grayFlag, value=0, createTime=1791532804707, updateTime=1791532804707, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175790465881, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=logo, value=https://castjournals.cast.org.cn/joweb/zyxb/CN/file/pic?fileId=vxJwzD/oKgABLDx+COUqfw==, createTime=1791532804677, updateTime=1791532804677, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175954043746, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=minRunFlag, value=0, createTime=1791532804716, updateTime=1791532804716, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175849186140, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zyxb/CN/file/pic, createTime=1791532804691, updateTime=1791532804691, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175941460833, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=silenceFlag, value=0, createTime=1791532804713, updateTime=1791532804713, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175832408923, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1791532804687, updateTime=1791532804687, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175882740574, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=themeColor, value=null, createTime=1791532804699, updateTime=1791532804699, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347175895323487, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346106557518446, code=themeStyle, value=null, createTime=1791532804702, updateTime=1791532804702, creator=18614031015, updator=18614031015)]), Website(id=1315346107010503292, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1315121837170065538, 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/zyxb/EN, language=EN, createTime=1791532549860, createBy=18614031015, updateTime=1791532762834, updateBy=18614031015, name=中医学报-英文, tplId=1146101810881728533, title=Acta Chinese Medicine, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1315347133386052431, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=articleTextType, value=kx, createTime=1791532794567, updateTime=1791532794567, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133339915084, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=banner, value=null, createTime=1791532794556, updateTime=1791532794556, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133427995474, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=grayFlag, value=0, createTime=1791532794577, updateTime=1791532794577, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133318943563, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=logo, value=https://castjournals.cast.org.cn/joweb/zyxb/EN/file/pic?fileId=vxJwzD/oKgABLDx+COUqfw==, createTime=1791532794551, updateTime=1791532794551, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133448966996, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=minRunFlag, value=0, createTime=1791532794582, updateTime=1791532794582, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133369275214, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zyxb/EN/file/pic, createTime=1791532794563, updateTime=1791532794563, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133440578387, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=silenceFlag, value=0, createTime=1791532794580, updateTime=1791532794580, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133360886605, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1791532794561, updateTime=1791532794561, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133411218256, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=themeColor, value=null, createTime=1791532794573, updateTime=1791532794573, creator=18614031015, updator=18614031015), WebsiteProps(id=1315347133419606865, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1315346107010503292, code=themeStyle, value=null, createTime=1791532794575, updateTime=1791532794575, creator=18614031015, updator=18614031015)])], journalTitle=中医学报, weixinUrl=null, journalUrl=https://hnzk.publish.founderss.cn/, iacademicId=null, status=1, seqNo=null, journalTitleEn=Acta Chinese Medicine, journalPhotoCn=8b94oSAFH8bu+kilqGRUOQ==, journalPhotoEn=Y56h/oCYJegF4hgM5ASRZw==, 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/zyxb/CN/10.16368/j.issn.1674-8999.2025.12.415, detailUrlEn=https://castjournals.cast.org.cn/joweb/zyxb/EN/10.16368/j.issn.1674-8999.2025.12.415, pdfUrlCn=https://castjournals.cast.org.cn/joweb/zyxb/CN/PDF/10.16368/j.issn.1674-8999.2025.12.415, pdfUrlEn=https://castjournals.cast.org.cn/joweb/zyxb/EN/PDF/10.16368/j.issn.1674-8999.2025.12.415, aliStartDate=0, aliEndDate=0, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=1, orderTime=1765296000000, fullTextJson=null, articleText=null, reference=null)
收藏切换
基于p53/p21通路探讨左归丸抑制细胞衰老保护帕金森病小鼠的作用机制
收藏切换
PDF下载
徐进 1 , 杨东东 2 , 李毛 1
中医学报 | 实验研究 2025,40(12): 2668-2677
收起
收藏切换
中医学报 |实验研究 2025 , 40 (12) : 2668 -2677
基于p53/p21通路探讨左归丸抑制细胞衰老保护帕金森病小鼠的作用机制
全屏
[Author(id=1315688485256810780, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, 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=1315688485344891166, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485256810780, language=EN, stringName=Jin XU, firstName=Jin, middleName=null, lastName=XU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1315688485424582943, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485256810780, language=CN, stringName=徐进, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1河南中医药大学第一附属医院，河南 郑州 450000, bio={"content":"

徐进（1980 -），男，河南驻马店人，医学硕士，副主任医师，研究方向：中医药防治帕金森病。

"}, bioImg=null, bioContent=

徐进（1980 -），男，河南驻马店人，医学硕士，副主任医师，研究方向：中医药防治帕金森病。

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1315688485084844309, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=1, ext=[AuthorCompanyExt(id=1315688485093232918, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000), AuthorCompanyExt(id=1315688485105815831, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1河南中医药大学第一附属医院，河南 郑州 450000)])]), Author(id=1315688485483303201, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, 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=1315688485558800675, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485483303201, language=EN, stringName=Dongdong YANG, firstName=Dongdong, middleName=null, lastName=YANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2The Affiliated Hospital to Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan China 610075, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1315688485625909540, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485483303201, language=CN, stringName=杨东东, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2成都中医药大学附属医院，四川 成都 610075, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1315688485177119000, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=2, ext=[AuthorCompanyExt(id=1315688485189701913, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485177119000, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2The Affiliated Hospital to Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan China 610075), AuthorCompanyExt(id=1315688485193896218, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485177119000, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2成都中医药大学附属医院，四川 成都 610075)])]), Author(id=1315688485697212710, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=1378172347@qq.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1315688485772710184, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485697212710, language=EN, stringName=Mao LI, firstName=Mao, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1315688485844013353, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, authorId=1315688485697212710, language=CN, stringName=李毛, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1河南中医药大学第一附属医院，河南 郑州 450000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1315688485084844309, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, xref=1, ext=[AuthorCompanyExt(id=1315688485093232918, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000), AuthorCompanyExt(id=1315688485105815831, tenantId=1146029695717560320, journalId=1315121837170065538, articleId=1315688480940871924, companyId=1315688485084844309, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1河南中医药大学第一附属医院，河南 郑州 450000)])])]
徐进1, 杨东东2, 李毛1
作者信息
  • 1河南中医药大学第一附属医院，河南 郑州 450000
  • 2成都中医药大学附属医院，四川 成都 610075
通讯作者:
李毛（1986 -），男，河南驻马店人，医学博士，研究方向：中医药防治帕金森病。E -mail:
作者简介:

徐进（1980 -），男，河南驻马店人，医学硕士，副主任医师，研究方向：中医药防治帕金森病。

Action Mechanism of Zuogui Pill Inhibiting Cellular Senescence and Protecting Parkinson′s Disease Mice Based on p53/p21 Pathway
Jin XU1, Dongdong YANG2, Mao LI1
Affiliations
  • 1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou Henan China 450000
  • 2The Affiliated Hospital to Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan China 610075
出版时间: 2025-12-10 doi: 10.16368/j.issn.1674-8999.2025.12.415
文章导航
收藏切换
摘要
收起

目的：基于p53/p21通路探讨左归丸对帕金森病（Parkinson's disease，PD）小鼠的脑保护作用机制。方法：采用随机数字表法将60只雄性C57BL/6小鼠分为对照组、模型组、左归丸低剂量组（1.8 g·kg-1·d-1）、左归丸中剂量组（3.6 g·kg-1·d-1）、左归丸高剂量组（7.2 g·kg-1·d-1）、美多芭组（50 mg·kg-1·d-1）。除对照组外，其余各组小鼠均通过腹腔注射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·d-1）建立PD模型，连续5d。从造模第1天起，各给药组同步开始灌胃给药，每日1次，持续10 d。采用行为学评估、免疫组化、Western Blot、Elisa、β-半乳糖苷酶（β-galactosidase，SA-β-gal）染色、免疫荧光染色法观察左归丸对PD小鼠细胞衰老的影响。结果：旷场实验结果显示，与对照组比较，模型组小鼠旷场运动总距离缩短（P＜0.01）；与模型组比较，左归丸中剂量组、左归丸高剂量组及美多芭组小鼠运动总距离增加（P＜0.01）。爬杆实验结果显示，与对照组比较，模型组小鼠爬杆时间延长（P＜0.05）；与模型组比较，左归丸高剂量组爬杆时间缩短（P＜0.05）。免疫组织化学染色及Western Blot法检测酪氨酸羟化酶（tyrosine hydroxylase，TH）蛋白结果显示，与对照组比较，模型组TH蛋白表达降低（P＜0.01）；与模型组比较，左归丸中剂量组、左归丸高剂量组及美多芭组TH蛋白表达升高（P＜0.05或P＜0.01）。Elisa结果显示，与对照组比较，模型组黑质组织和纹状体组织多巴胺（dopamine，DA）、二羟基苯基乙酸（dihydroxy -phenyl acetic acid，DOPAC）、高香草酸（homovanillic acid，HVA）水平降低（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织和纹状体组织DA、DOPAC、HVA水平均升高（P＜0.05或P＜0.01）。免疫荧光双染检测结果显示，与对照组比较，模型组核纤层蛋白B1（nuclear lamina protein B1，Lamin B1）阳性细胞数减少（P＜0.01），胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）阳性细胞数增加（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组Lamin B1阳性细胞数增加（P＜0.05或P＜0.01），GFAP阳性细胞数减少（P＜0.01）。Western blot检测结果显示，与对照组比较，模型组黑质组织p53（tumour protein 53，TP53）、细胞周期蛋白依赖性激酶抑制剂1A（Cyclin-dependent kinase inhibitor 1A，CDKN1A，p21）、细胞周期蛋白依赖性激酶抑制剂2A（Cyclin-dependent kinase inhibitor 2A，CDKN2A，p16）蛋白表达均升高（P＜0.01）；与模型组相比，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织p53、p21、p16蛋白表达均降低（P＜0.01）。SA-β-gal染色法结果显示，与对照组比较，模型组黑质组织SA-β-gal蛋白阳性表达面积增加（P＜0.01）；与模型组相比，左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织SA-β-gal蛋白阳性表达面积降低（P＜0.05或P＜0.01）。Elisa检测结果显示，与对照组比较，模型组黑质组织IL-6、IL-8水平均升高（P＜0.01）；与模型组相比，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组黑质组织IL-6、IL-8水平均降低（P＜0.05或P＜0.01）。结论：左归丸可能通过抑制p53/p21通路，减轻细胞衰老，从而对PD模型小鼠发挥保护作用。

左归丸  /  细胞衰老  /  帕金森病  /  p53/p21通路

Objective:To explore the neuroprotective mechanism of Zuogui Pills in Parkinson's disease（PD）mice based on the p53/p21 pathway.Methods:Sixty male C57BL/6 mice were randomly divided into a control group，model group，low-dose Zuogui Pills group（1.8 g·kg-1·d-1），medium-dose Zuogui Pills group（3.6 g·kg-1·d-1），high-dose Zuogui Pills group（7.2 g·kg-1·d-1），and Madopar group（50 mg·kg-1·d-1）using a random number table method.Except for the control group，all other groups were modeled by intraperitoneal injection with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine（MPTP）（30 mg·kg-1·d-1）for five consecutive days.From the first day of modeling，the treatment groups were administered orally once daily for 10 days. Behavioral assessment，immunohistochemistry，Western Blot，ELISA，β-galactosidase（SA-β-gal）staining，and immunofluorescence staining were used to observe the effect of Zuogui Pills on cellular senescence in PD mice.Results:The open field test results showed that，compared with the control group，the total distance traveled by mice in the model group was reduced（P＜0.01）；compared with the model group，the total distance traveled by mice in the medium-dose and high-dose Zuogui Pill groups，as well as the Madopar group，was increased（P＜0.01）.The pole-climbing test results showed that，compared with the control group，the time for mice in the model group to climb the pole was prolonged（P＜0.05）；compared with the model group，the pole -climbing time was shortened in the high-dose Zuogui Pill group（P＜0.05）.Immunohistochemistry and Western Blot detection of tyrosine hydroxylase（TH）protein showed that，compared with the control group，TH protein expression in the model group was decreased（P＜0.01）；compared with the model group，TH protein expression was increased in the medium-dose and high-dose Zuogui Pill groups，as well as in the Madopar group（P＜0.05 or P＜0.01）.ELISA results showed that，compared with the control group，the levels of dopamine（DA），dihydroxy-phenyl acetic acid（DOPAC），and homovanillic acid（HVA）in the substantia nigra and striatum tissues of the model group were decreased（P＜0.01）；compared with the model group，the levels of DA，DOPAC，and HVA in the substantia nigra and striatum tissues were increased in the low-dose，medium-dose，and high-dose Zuogui Pill groups，as well as in the Madopar group（P＜0.05 or P＜0.01）.Immunofluorescence double staining results showed that compared with the control group，the number of Lamin B1（nuclear lamina protein B1）positive cells in the model group was reduced（P＜0.01），and the number of GFAP（glial fibrillary acidic protein）positive cells was increased（P＜0.01）. Compared with the model group，the numbers of Lamin B1 positive cells in the low-dose，medium-dose，and high-dose Zuogui pills groups，as well as in the Madopar group，were increased（P＜0.01），while the numbers of GFAP positive cells were decreased（P＜0.05 or P＜0.01）.Western blot results showed that compared with the control group，the protein levels of p53（tumor protein 53，TP53），CDKN1A（Cyclin-dependent kinase inhibitor 1A，p21），and CDKN2A（Cyclin-dependent kinase inhibitor 2A，p16）in the substantia nigra tissue of the model group were all elevated（P＜0.01）. Compared with the model group，the protein levels of p53，p21，and p16 in the substantia nigra tissue were reduced in the low-dose，medium-dose，and high-dose Zuogui pills groups，as well as in the Madopar group（P＜0.01）.SA-β-gal staining results showed that compared with the control group，the area of SA-β-gal positive expression in the substantia nigra tissue of the model group was increased（P＜0.01）；compared with the model group，the area of SA-β-gal positive expression was decreased in the medium-dose and high-dose Zuogui pills groups，as well as in the Madopar group（P＜0.05 or P＜0.01）.ELISA results showed that compared with the control group，the levels of IL-6 and IL-8 in the substantia nigra tissue of the model group were increased（P＜0.01）；compared with the model group，the levels of IL-6 and IL-8 in the substantia nigra tissue were reduced in the low-，medium-，and high-dose Zuogui Pill groups，as well as in the Madopar group（P＜0.05 or P＜0.01）. Conclusion:Zuogui Pill may exert a protective effect on PD model mice by alleviating cellular senescence through inhibition of the p53/p21 pathway.

Zuogui Pill  /  cellular senescence  /  Parkinson's disease  /  p53/p21 pathway
徐进, 杨东东, 李毛. 基于p53/p21通路探讨左归丸抑制细胞衰老保护帕金森病小鼠的作用机制. 中医学报, 2025 , 40 (12) : 2668 -2677 . DOI: 10.16368/j.issn.1674-8999.2025.12.415
Jin XU, Dongdong YANG, Mao LI. Action Mechanism of Zuogui Pill Inhibiting Cellular Senescence and Protecting Parkinson′s Disease Mice Based on p53/p21 Pathway[J]. Acta Chinese Medicine, 2025 , 40 (12) : 2668 -2677 . DOI: 10.16368/j.issn.1674-8999.2025.12.415
正文
收起
帕金森病（Parkinson's disease，PD）又称震颤麻痹病，由英国医师James Parkinson于1817年在他的经典之作《关于震颤麻痹的评论》（An essay on the shaking palsy）中首次提出。PD主要表现为运动迟缓、肌僵直、静止性震颤以及姿势不稳等运动症状，并常伴有感觉障碍、精神行为异常、认知障碍、睡眠障碍以及自主神经功能障碍等非运动症状[1-2]。目前我国有超过270万例PD患者，预计到2030年将激增至500万，占全世界PD患者总数的50%以上[3]。PD的高发病率、高致残率严重影响患者身体健康和生活质量，给社会和家庭带来沉重的经济负担。目前，PD的主要治疗药物为多巴类制剂，但这些药物不能改变疾病的病理发展或阻止疾病的进展[4]。细胞衰老是机体衰老的标志，衰老细胞持续存在于组织中，它们会引起局部炎症，并对周围细胞有害，进而导致机体老化和功能障碍，在PD的发病中起着至关重要的作用。有研究显示，环鸟苷酸-腺苷酸合成酶/干扰素基因刺激因子/脂质运载蛋白2（cGAS/STING/LCN2）通路能调控星形胶质细胞衰老，从而影响PD的发展[5]。另有研究显示，通过促进小鼠黑质细胞铁超载和细胞衰老，可导致小鼠运动障碍[6]。因此，阻止细胞衰老可能是未来有效治疗PD的新方法。
左归丸出自《景岳全书》，为补肾益精、滋补肾阴要方。由六味地黄丸减泽泻、茯苓、牡丹皮，加枸杞子、川牛膝、菟丝子、龟板胶、鹿角胶化裁而来。有研究显示，左归丸能改善肝肾阴虚型PD运动症状与非运动症状[7]，然而其治疗PD的具体机制尚不清楚。左归丸还能抗衰老、改善衰老大鼠学习记忆能力[8]。笔者根据《素问·至真要大论》:“七八……精少，肾脏衰，形体皆极”，提出“肾衰形极”是PD运动障碍的根本原因，并应用左归丸补肾益精改善PD运动障碍。p53是一种细胞衰老调节因子，p53通过激活p21导致细胞周期停滞和细胞衰老。本研究发现，左归丸可能通过p53/p21通路抑制黑质星形胶质细胞衰老，进而减少PD小鼠模型多巴胺能神经元死亡，为未来PD的治疗提供新的药物及作用靶点。
1　材料
收起
1.1　动物
10～12周龄SPF级健康雄性C57BL/6小鼠，体质量24～30 g，购于成都达硕实验动物有限公司，合格证号SCXK（川）2020 -030。饲养于成都中医药大学实验动物中心标准化动物房。实验环境通风、安静，自由进食和饮水，相对湿度控制在（50 ±5）%，温度（23 ±2）℃，光照时长控制在12h（8∶00—20∶00光照；20∶00—8∶00黑暗）。所有实验程序均在成都中医药大学动物实验伦理委员会的指导下进行，伦理审查号为20211498A。
1.2　药物与试剂
左归丸（仲景宛西制药股份有限公司，批号Z41020696）；1 -甲基-4 -苯基-1，2，3，6-四氢吡啶（1 -methyl-4 -phenyl-1，2，3，6-tetrahydropyridine，MPTP）（MACKLIN，批号：C12450723）；美多芭（上海罗氏制药，批号：SH5057）；酪氨酸羟化酶（tyrosine hydroxylase，TH）、p53、p21抗体（proteintech，批号分别为25859 -1 -AP、60283-2-Ig、10355-1 -AP）；核纤层蛋白B1（nuclear lamin protein B1，lamin B1）抗体（三鹰，批号12987-1-AP）；p16（abcam，批号ab51243）；β-actin、GAPDH（abclonal，批号分别为AC026、AC033）；胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）抗体、CY3标记山羊抗兔IgG二抗、辣根过氧化物酶（horseradish peroxidase，HRP）标记山羊抗兔IgG二抗（武汉塞维尔生物科技有限公司，批号分别为GB11096、GB21303、GB23303）；多巴胺（dopamine，DA）、二羟苯基乙酸（dihydroxy-phenyl acetic acid，DOPAC）、高香草酸（homovanillic acid，HVA）、白细胞介素-6（interleukin-6，IL-6）、白细胞介素-8（interleukin-8，IL-8）酶联免疫吸附法（ELISA）检测试剂盒（上海茁彩生物科技有限公司，批号分别为ZC-38119、ZC-56579-J、ZC-56552-J、ZC-37988、ZC-37935）。
1.3　仪器
SpectraMAX Plus384型酶标仪（美谷分子仪器有限公司），KZ -III -F型高速低温组织研磨仪（武汉赛维尔生物科技有限公司），RM2016型石蜡切片机（上海徕卡仪器有限公司），BMJ-Ⅲ型包埋机（常州郊区中威电子仪器厂），S1010E型掌上离心机（美国SCLOGEX公司），H2050R型台式高速冷冻离心机（湘仪集团），HH -6型恒温水浴锅（上海力辰邦西仪器科技有限公司），BA410型显微镜（麦克奥迪实业集团有限公司）。
2　方法
收起
2.1　药物制备
用无菌生理盐水将左归丸配制成125 g·L-1的浓度。
2.2　分组、造模与给药
适应性喂养1周，采用随机数字表法将小鼠随机分为6组，每组10只。分别为对照组、模型组、左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组。根据文献[9-11]中的方法，用无菌生理盐水配制成质量浓度为2 g·L-1的MPTP，对照组给予等容量的无菌生理盐水每天腹腔注射，其余各组每天腹腔注射30 mg·kg-1的MPTP，均连续注射5d。注射MPTP 90 min后，观察实验小鼠行为变化，当表现为动作笨拙、肢体僵硬、震颤、步态不稳、竖毛及反应迟钝，即表示造模成功。自造模的第1天开始给药，于MPTP处理1h后给予左归丸灌胃。对照组和模型组给予等容量的无菌生理盐水灌胃。根据前期实验[11]及文献[12]，左归丸低、中、高剂量组分别以1.8 g·kg-1·d-1、3.6 g·kg-1·d-1、7.2 g·kg-1·d-1左归丸灌胃，美多芭组给予50 mg·kg-1·d-1美多芭灌胃。连续给药10 d（即MPTP停止注射后再灌胃5d）。
2.3　样本制备
给药结束次日，行为学评估后断头处死小鼠，于4 ℃冰块上迅速取黑质纹状体区组织块。
2.4　行为学评估
2.4.1　旷场实验
取一长70 cm、宽70 cm、高30 cm的旷场装置，将实验小鼠轻轻置放在旷场装置某一固定方位的角落处，摄像机记录小鼠行动轨迹，连续观测5 min。
2.4.2　爬杆实验
取一直径为1 cm、长40 cm木杆垂直放置，木杆顶端固定一直径2.5 cm的球形突起，记录小鼠从顶端前肢爬至底部时间。每组重复测量3次，取平均值。
2.5　免疫组织化学染色检测TH蛋白表达
4%的多聚甲醛溶液中固定组织12 h，经全自动脱水机脱水，切片60 ℃烘烤1h，切片脱蜡至水，常温保存。将脑片置于柠檬酸盐缓冲液（pH 6.0），修复仪100 ℃，修复20 min，冷却后，PBS洗3次，每次5 min。山羊血清封闭液，室温封闭20 min，滴加一抗，在4 ℃过夜；PBS冲洗3次，再滴加二抗孵育，37 ℃下30 min；配置新鲜DAB显色液，滴加到脑组织上，室温显色；苏木素复染3 min，自来水洗，清水返蓝后流水冲洗；将切片依次置于75%、85%、95%、无水乙醇、二甲苯中分别浸泡10 min，中性树胶封片。
2.6　Western Blot法检测TH、p53、p21、p16蛋白表达
取黑质组织放入2mL研磨管中，然后向每管加入2颗3mm研磨珠及RIPA裂解液，在高速低温组织研磨仪内研磨4次，取出放4 ℃冰箱30 min进行裂解。离心机离心，收集上清液，BCA蛋白定量试剂盒测定蛋白浓度。于SDS凝胶上电泳，并转移到PVDF膜上。随后，将膜在含有5%脱脂乳的TBST中浸泡，室温下摇床封闭2h。将PVDF膜放入一抗中（1∶1 000），4 ℃孵育过夜；TBST冲洗，放入二抗中（1∶5 000），室温孵育2 h TBST冲洗。在避光环境下把PVDF膜完全浸没在含有ECL混合液的培养皿中，曝光。
2.7　Elisa法检测DOPAC、HVA、DA、IL-6、IL-8水平
收集组织样本，以质量体积比1∶9加入PBS，组织研磨仪进行组织匀浆，5 000 ×g离心10 min，取上清液。试剂盒室温平衡30 min，标准品孔各加不同浓度的标准品50 μL，样本孔中加入待测样本50 μL。空白孔不加，标准品孔和样本孔中每孔加入HRP标记的检测抗体100 μL，封孔，37 ℃恒温箱温育60 min。洗涤，吸水纸上拍干，反复5次。每孔加入底物A、B各50 μL，37 ℃避光孵育15 min。每孔加入终止液50 μL，10 min，在450 nm波长处测定各孔的OD值。
2.8　染色法检测 β-半乳糖苷酶（β-galactosidase，SA-β-gal）蛋白表达
石蜡切片置于65 ℃恒温箱烘烤1h，脱蜡，加入SA-β-gal染色固定液固定30 min，去除固定液，PBS洗3次，加入适当SA-β-gal染色液，37 ℃孵育过夜。弃液脱水封片，光镜下拍照观察。
2.9　免疫荧光共定位观察中脑黑质GFAP、Lamin B1阳性细胞数
依次将切片放入脱蜡液Ⅰ15 min，二甲苯Ⅱ 15 min，二甲苯Ⅲ 15 min，无水乙醇Ⅰ5 min；无水乙醇Ⅱ5 min，85%酒精5 min，75%酒精5 min，蒸馏水洗。抗原修复，牛血清，室温孵育30 min；加入一抗，4 ℃过夜，PBS洗3次，每次5 min。加入二抗，室温孵育50 min；PBS洗涤3次，每次5 min。滴加DAPI，室温孵育10 min；PBS洗3次，每次5 min。抗荧光淬灭封片剂封片。荧光显微镜下采集图像。
2.10　统计学分析
本次实验结果采用GraphPad Prism 9.0软件进行数据统计分析，计量资料数据以均数±标准差（±s）表示。符合正态分布的数据，多组间比较采用单因素方差分析（one-way ANOVA），两两比较若方差齐性采用LSD检验，方差不齐则采用Tamhane's T2检验；不符合正态分布的数据，采用非参数秩和检验。P＜0.05为差异有统计学意义。
3　结果
收起
3.1　左归丸对PD小鼠行为学的影响
当给予MPTP腹腔注射后，C57BL/6小鼠出现动作笨拙、肢体僵硬、震颤、步态不稳、竖毛及反应迟钝，与PD患者的临床表现相似。与对照组比较，模型组小鼠旷场运动总距离缩短（P＜0.01）；与模型组比较，左归丸中剂量组、左归丸高剂量组及美多芭组小鼠运动总距离增加（P＜0.01）。与对照组比较，模型组小鼠爬杆时间延长（P＜0.05）；与模型组比较，左归丸高剂量组爬杆时间缩短（P＜0.05）。这些结果表明，左归丸能改善MPTP诱导的PD小鼠的行为障碍，见表1、图1。
3.2　左归丸对黑质、纹状体TH蛋白表达的影响
免疫组织化学技术及Western Blot法检测TH蛋白表达。结果显示，与对照组比较，模型组TH蛋白表达降低（P＜0.01）。与模型组比较，左归丸中剂量组、左归丸高剂量组及美多芭组TH蛋白表达升高（P＜0.05，P＜0.01），见图2、表2。
3.3　左归丸对黑质组织DA、DOPAC、HVA水平的影响
Elisa检测黑质组织DA、DOPAC、HVA含量。结果显示，与对照组比较，模型组DA、DOPAC、HVA水平降低（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组DA、DOPAC、HVA水平均升高（P＜0.05或P＜0.01）；且随着左归丸剂量的增加，这一升高趋势更加明显，见表3。
3.4　左归丸对纹状体组织DA、DOPAC、HVA水平的影响
ELISA检测纹状体组织DOPAC、HVA、DA含量。结果显示，与对照组比较，模型组DA、DOPAC、HVA水平降低（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组DA、DOPAC、HVA水平均升高（P＜0.05或P＜0.01）；且随着左归丸剂量的增加，升高趋势更加明显，见表4。
3.5　左归丸对黑质组织Lamin B1、GFAP阳性细胞数的影响
免疫荧光双染检测Lamin B1、GFAP，结果显示，与对照组比较，模型组Lamin B1阳性细胞数减少（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组Lamin B1阳性细胞数增加（P＜0.05或P＜0.01）。与对照组比较，模型组GFAP阳性细胞数增加（P＜0.01）；与模型组比较，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组GFAP阳性细胞数减少（P＜0.01）；且随着左归丸剂量的增加，减少趋势更加明显，见图3、表5。
3.6　左归丸对黑质组织p53、p21、p16蛋白表达的影响
中脑黑质组织Western blot检测结果显示，与对照组比较，模型组p53、p21、p16蛋白表达均升高（P＜0.01）。与模型组相比，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组p53、p21、p16蛋白表达均降低（P＜0.01）；且随着左归丸剂量的增加，降低趋势更加明显，见图4、表6。
3.7　左归丸对黑质组织SA-β-gal蛋白表达的影响
SA-β-gal染色法检测黑质组织SA-β-galSA-β-gal蛋白表达。结果显示，与对照组比较，模型组SA -β-gal蛋白阳性表达面积增加（P＜0.01）；与模型组相比，左归丸中剂量组、左归丸高剂量组、美多芭组SA-β-gal蛋白阳性表达面积降低（P＜0.05或P＜0.01），见图5、表7。
3.8　左归丸对黑质组织IL-6、IL-8水平的影响
Elisa检测黑质组织IL -6、IL -8含量。结果显示，与对照组比较，模型组IL-6、IL-8水平均升高（P＜0.01）；与模型组相比，左归丸低剂量组、左归丸中剂量组、左归丸高剂量组、美多芭组IL -6、IL-8水平均降低（P＜0.05或P＜0.01）；且随着左归丸剂量的增加，降低势更加明显。见表8。
4　讨论
收起
PD属中医学“颤证”“拘病”范畴。“肾衰形极”是PD运动障碍发生的根本原因。《素问·至真要大论》云：“七八……天癸竭，精少，肾脏衰，形体皆极。”指出肾精在维持形体活动中的重要作用。肾主生长发育，人体也随着肾精盛衰而经历生、长、壮、老、已的生命过程。肾藏先天之精和五脏六腑之精，肾所藏元精是人体生命运动的根本动力，对于维持人体机能活动起着至关重要的作用。肾为“性命之根”，肾精虚衰是衰老的根本。“足于精者，百病不生”，肾精虚衰则四肢百骸失于濡养，脏腑功能减退，病理产物堆积，导致老年相关疾病发生。《医学正传》记述“肾气盛则寿延，肾气衰则寿夭”。《医学入门》曰：“人至中年，肾气自衰。”人年过半百，则阴气自半，肾居下焦属阴，随着年岁的增长，肾脏功能衰退，阴精不足，不能濡养形体脑窍，就会出现动作缓慢，四肢灵活度降低，行则偻俯，记忆力减退等机体衰老症状。朱丹溪认为人体“阳常有余而阴不足”，肾中阴精不足，相火妄动，则常伴有肢体震颤症状。明代赵献可在《医贯·痰论》中亦指出本病由“肾虚不能制水，则水不归源”；清代张璐明确指出颤振乃“肾虚而行步振掉”，指出PD由肾虚导致。临床治疗PD时，常加用补益肝肾的方药。左归丸具有补肾滋阴益精作用，肾精充足则四肢百骸得以濡养，灵活有力。本研究显示，左归丸能改善PD运动障碍，缩短小鼠爬杆时间，增加旷场活动的总距离。
DA是一种儿茶酚胺类神经递质，主要产生于黑质腹侧被盖区。酪氨酸是合成DA的原料，TH是合成DA的关键限速酶。脑内TH含量的变化直接影响黑质-纹状体系统中DA的生物合成[13]。DA单胺类氧化酶代谢途径最后代谢为DOPAC，经儿茶酚胺-O -甲基转移酶途径最后代谢为HVA[14]。在本研究中，腹腔注射MPTP后降低了小鼠黑质-纹状体TH、DA、DOPAC、HVA含量，导致帕金森病样症状。左归丸可以显著增加PD小鼠TH、DA、DOPAC、HVA含量，逆转MPTP引起的多巴胺神经元数量损伤，改善PD小鼠运动障碍。
星形胶质细胞是中枢神经系统中分布最广、体积最大的胶质细胞[15]。星形胶质细胞发出众多突起，延续包裹在神经细胞胞体及突起。神经元在有丝分裂后不太可能经历传统的衰老诱导，然而衰老可优先发生在星形胶质细胞内。星形胶质细胞为神经元提供结构、代谢和营养支持，当衰老的星形胶质细胞采用促炎分泌表型时，会损害神经元功能，并在体内导致与衰老相关的神经变性和脑功能下降[5，16-17]。脑损伤后，能够有丝分裂的星形胶质细胞在一个称为反应性星形胶质细胞增生的过程中发生分子、细胞和功能变化。相关研究表明，星形胶质细胞在神经退行性疾病中具有重要作用[18-19]。有研究显示，衰老的星形胶质细胞积聚，影响神经元功能，与神经退行性变和认知和运动障碍有关[20]。GFAP主要分布在中枢神经系统的星形胶质细胞；Lamin B1是维持细胞核完整性的关键组分，参与细胞的增殖与衰老，细胞衰老时Lamin B1的表达下降[21]。本研究中，MPTP诱导的小鼠模型黑质GFAP阳性细胞数增加，Lamin B1阳性细胞数减少，左归丸可以逆转MPTP引起的这一过程，减轻星形胶质细胞损伤。
细胞衰老是机体衰老的标志，衰老细胞的积累会促进机体老化和功能障碍，而消除衰老细胞则有望延年益寿。移植相对少量的衰老细胞会加速健康年轻小鼠的衰老，而减少小鼠衰老细胞负荷可以减轻衰老特征，带来健康益处，并延长老年动物的寿命[22]。由于衰老细胞持续存在于组织中，它们会引起局部炎症并对周围细胞有害[23-24]，从而导致人体衰老。神经退行性疾病如帕金森病，是衰老性疾病，多巴胺神经元的衰老是PD的主要促进因素[25]，而CD8 +T淋巴细胞是一种重要的免疫细胞，这种免疫细胞的“异常”老化可能有助于PD的发展[26]。p16是一种被广泛接受的人体衰老和细胞衰老标记物，随着年龄的增长该标志物在神经或肌肉干细胞表达明显增加。有研究显示p16在PD患者黑质致密部表达增高[27]，表明PD多巴胺能神经元存在细胞衰老。p21是另一种CDK抑制剂，在细胞衰老过程中，应激诱导的p53通过激活p21导致细胞周期阻滞。衰老相关SA-β-gal是一种溶酶体水解酶，是当今用于检测衰老细胞最广泛使用的生物标志物，在细胞衰老过程中SA-β-gal特异性升高[28]。衰老相关分泌表型（senescence -associated secretory phenotype，SASP）将衰老细胞转化为促炎介质、活性氧和金属蛋白酶的连续来源。衰老细胞可能维持促炎环境，这可能对邻近细胞造成损害，将邻近细胞转化为衰老细胞。炎性介质是SASP的重要组成成分，也是细胞衰老的关键特点。IL-6与IL-8是主要的SASP介质，在老年大脑和AD中上调，其过表达在体内驱动神经退行性变。本研究发现，MPTP诱导的小鼠模型黑质中p53、p21、p16、SA-β-gal蛋白表达均升高，IL-6、IL-8水平均升高；经左归丸治疗后这些指标均降低，且随着左归丸剂量增加，这一效果更加明显。表明左归丸能够改善PD小鼠黑质组织细胞衰老，可能与p53/p21通路有关。
综上所述，左归丸可改善PD模型小鼠运动障碍，其作用机制可能与抑制p53/p21通路，阻止星形胶质细胞衰老，进而减少多巴胺神经元损伤有关。

文献
收起
参考文献 引证文献
排序方式：
[1]
MORRIS H R, SPILLANTINI M G, SUE C M, et al. The pathogenesis of Parkinson's disease[J]. Lancet, 2024, 403(10423):293-304.
[2]
TANNER C M, OSTREM J L. Parkinson's Disease[J]. N Engl J Med, 2024, 391(5):442-452.
[3]
ROSSI A, BERGER K, CHEN H, et al. Projection of the prevalence of Parkinson's disease in the coming decades:Revisited[J]. Mov Disord, 2018, 33(1):156-159.
[4]
徐进,张怀亮,杨东东, 等. 莫诺苷抑制铁死亡保护MPP +诱导的PC12细胞模型的机制研究[J]. 中医研究, 2024, 37(6):75-82.
[5]
JIANG S Y, TIAN T, YAO H, et al. The cGAS-STING-YY1 axis accelerates progression of neurodegeneration in a mouse model of Parkinson's disease via LCN2-dependent astrocyte senescence[J]. Cell Death Differ, 2023, 30(10):2280-2292.
[6]
SHEN Q Q, JV X H, MA X Z, et al. Cell senescence induced by toxic interaction between α-synuclein and iron precedes nigral dopaminergic neuron loss in a mouse model of Parkinson's disease[J]. Acta Pharmacol Sin, 2024, 45(2):268-281.
[7]
苏文理,张丽梅,纪家镛, 等. 左归丸加减治疗肝肾阴虚型帕金森病临床观察[J]. 光明中医, 2021, 36(13):2204-2206.
[8]
姚建平,李琳,牛巧能, 等. 左归丸对自然衰老大鼠海马乙酰胆碱含量及学习记忆功能的影响[J],中成药, 2018, 40(1):181-183.
[9]
JANKOVIC J, TAN E K. Parkinson's disease:etiopathogenesis and treatment[J]. J Neurol Neurosurg Psychiatry, 2020, 91(8):795-808.
[10]
李毛,兰瑞,杨东东, 等. 莫诺苷通过Nrf2/ARE通路抑制铁死亡对帕金森病小鼠的保护作用[J]. 中成药, 2025, 47(4):1297-1304.
[11]
LI M, ZHANG J, JIANG L, et al. Neuroprotective effects of morroniside from Cornus officinalis sieb.Et zucc against Parkinson's disease via inhibiting oxidative stress and ferroptosis[J]. BMC Complement Med Ther, 2023, 23(1):218.
[12]
佟雷,刘金丽,孙琳林, 等. 左归丸及右归丸对卵巢早衰小鼠卵巢衰老的预防作用[J]. 中成药, 2017, 39(2):260-265.
[13]
SALVATORE M F, MCINNIS T R, CANTU M A, et al. Tyrosine Hydroxylase Inhibition in Substantia Nigra Decreases Movement Frequency[J]. Mol Neurobiol, 2019, 56(4):2728-2740.
[14]
LORENC-KOCI E, KAMI? SKA K, LENDA T, et al. The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5),Sildenafil,in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats[J]. Molecules, 2024, 29(18):4318.
[15]
FORREST S L, KIM J H, CROCKFORD D R, et al. Distribution Patterns of Astrocyte Populations in the Human Cortex[J]. Neurochem Res, 2023, 48(4):1222-1232.
[16]
YAN X, ZENG R, CAO Y. Astragaloside IV confronts amyloid-beta-induced astrocyte senescence via hsp90aa1[J]. J Appl Biomed, 2024, 22(3):129-135.
[17]
FANCY N N, SMITH A M, CARAMELLO A, et al. Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics[J]. Acta Neuropathol, 2024, 147(1):78.
[18]
BRANDEBURA A N, PAUMIER A, ONUR T S, et al. Astrocyte contribution to dysfunction,risk and progression in neurodegenerative disorders[J]. Nat Rev Neurosci, 2023, 24(1):23-39.
[19]
BADIA-SOTERAS A, MAK A, BLOK T M, et al. Astrocyte-synapse structural plasticity in neurodegenerative and neuropsychiatric diseases[J]. Biol Psychiatry, 2025, S0006-3223(25):01125-4.
[20]
WANG M, TIAN T, ZHOU H, et al. Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling[J]. J Neuroinflammation, 2024, 21(1):81.
[21]
MATIAS I, DINIZ L P, DAMICO I V, et al. Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus[J]. Aging Cell, 2022, 21(1):e13521.
[22]
JEON O H, MEHDIPOUR M, GIL T H, et al. Systemic induction of senescence in young mice after single heterochronic blood exchange[J]. Nat Metab, 2022, 4(8):995-1006.
[23]
WANG B, HAN J, ELISSEEFF J H, et al. The senescence-associated secretory phenotype and its physiological and pathological implications[J]. Nat Rev Mol Cell Biol, 2024, 25(12):958-978.
[24]
LAWRENCE M, GOYAL A, PATHAK S, et al. Cellular Senescence and Inflammaging in the Bone:Pathways,Genetics,Anti-Aging Strategies and Interventions[J]. Int J Mol Sci, 2024, 25(13):7411.
[25]
RIESSLAND M, KOLISNYK B, KIM T W, et al. Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons[J]. Cell Stem Cell, 2019, 25(4):514-530.e8.
[26]
WILLIAMS-GRAY C H, WIJEYEKOON R S, SCOTT K M, et al. Abnormalities of age-related T cell senescence in Parkinson's disease[J]. J Neuroinflammation, 2018, 15(1):166.
[27]
VERMA D K, SEO B A, GHOSH A, et al. Alpha-Synuclein Preformed Fibrils Induce Cellular Senescence in Parkinson's Disease Models[J]. Cells, 2021, 10(7):1694.
[28]
BULBIANKOVA D, DIAZ-PUERTAS R, ALVAREZ-MARTINEZ F J, et al. Hallmarks and Biomarkers of Skin Senescence:An Updated Review of Skin Senotherapeutics[J]. Antioxidants (Basel), 2023, 12(2):444.
2025年第40卷第12期
PDF下载
133
60
引用本文
BibTeX
文章信息
doi: 10.16368/j.issn.1674-8999.2025.12.415
  • 接收时间：2025-06-09
  • 首发时间：2026-10-10
  • 出版时间：2025-12-10
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2025-06-09
基金
作者信息
    1河南中医药大学第一附属医院，河南 郑州 450000
    2成都中医药大学附属医院，四川 成都 610075

通讯作者:

李毛（1986 -），男，河南驻马店人，医学博士，研究方向：中医药防治帕金森病。E -mail:
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/zyxb/CN/10.16368/j.issn.1674-8999.2025.12.415
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