Article(id=1322926110471758625, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.07.036, 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=1793339763515, onlineDateStr=2026-10-30, pubDate=1752076800000, pubDateStr=2025-07-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339763515, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339763515, creator=13701087609, updateTime=1793339763515, updator=13701087609, issue=Issue{id=1322925862630339452, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='7', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1752076800000', pubDateStr='2025-07-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339704424, creator='13701087609', updateTime=1793340532184, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929334587105328, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929334587105329, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=182, endPage=189, ext={EN=ArticleExt(id=1322926110723416866, articleId=1322926110471758625, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Screening of Effective Parts of Shenling Baizhu Powder(参苓白术散)for Improving Obese Type 2 Diabetes Mellitus, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To observe the effects of Shenling Baizhu Powder(参苓白术散,SLBZP)and its separated components on glucose and lipid metabolism in obese type 2 diabetes mellitus(T2DM)rats induced by high-fat diet(HFD)combined with low-dose streptozotocin(STZ),so as to obtain the best effective part of SLBZP to improve obese T2DM,and to clarify the main material basis of SLBZP to treat T2DM with“sweet drugs”.

Methods

The obese T2DM rats were treated with SLBZP,its split components and liraglutide. The body weight,abdominal circumference,food intake,water intake and fasting blood glucose of rats were measured regularly,and oral glucose tolerance test(OGTT),insulin tolerance test(ITT)and pyruvate tolerance test(PTT)were performed after administration. Homeostasis model assessment of insulin resistance index(HOMA-IR),homeostasis model assessment ofβ-cell(HOMA-β),insulin sensitivity index(ISI),quantitative insulin sensitivity check index(QUICKI)and other parameters were calculated. At the end of the study,the serum and pancreatic tissue were collected for biochemical and pathological analysis.

Results

The obese T2DM animal model was successfully established by HFD+STZ.SLBZP and its split components can reduce the weight and abdominal circumference of obese T2DM rats,alleviate the phenotype of polyphagia and polydipsia in obese T2DM rats,and regulate lipid metabolism. It can reduce fasting blood glucose,improve glucose tolerance,insulin tolerance and pyruvate tolerance,islet morphology and function,and regulate glucose metabolism in obese T2DM rats.

Conclusion

SLBZPand its separated components can effectively improve obese T2DM,regulate the disorder of glucose and lipid metabolism,and repair the pathological damage of pancreas. Polysaccharide of SLBZP is the best effective part to improve obese T2DM. The polysaccharides faction,70% ethanol fraction and water eluted fraction of SLBZPare the main material basis of the“sweet”taste of SLBZP,which together play the role of SLBZPin improving obese T2DM.

, authors=Kewei YANG1, 2, Lianlian ZHU1, 2, Shanshan YU1, 2, Zhengyuan CHEN3, Jin WU1, 2, Shuang WANG1, 2, Libin ZHAN1, 2, authorsList=Kewei YANG, Lianlian ZHU, Shanshan YU, Zhengyuan CHEN, Jin WU, Shuang WANG, Libin ZHAN, authorCompany=null, correspAuthors=Lianlian ZHU, Libin ZHAN, 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=1322926112816374583, articleId=1322926110471758625, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=参苓白术散改善肥胖2型糖尿病有效部位的筛选, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=
目的

观察参苓白术散(Shenling Baizhu Powder,SLBZP)及其拆分组分对高脂饮食(High fat diet,HFD)结合小剂量链脲佐菌素(Streptozotocin,STZ)所致肥胖2型糖尿病(Type 2 diabetes mellitus,T2DM)大鼠糖脂代谢的影响,从而获得参苓白术散改善肥胖2型糖尿病的最佳有效部位,并阐明参苓白术散以“甘”治“甘”的主要物质基础。

方法

采用参苓白术散及其拆分组分、利拉鲁肽治疗肥胖T2DM大鼠。定期测量大鼠的体质量、腹围、摄食量、饮水量、空腹血糖,给药结束后进行口服葡萄糖耐量试验(Oral glucose tolerance test,OGTT)、胰岛素耐量试验(Insulin tolerance test,ITT)、丙酮酸耐量试验(Pyruvate tolerance test,PTT)。计算稳态模型-胰岛素抵抗指数(Homeostasis model assessment of insulin resistance index,HOMA-IR)、稳态模型胰岛素分泌指数(Homeostasis model assessment ofβ-cell,HOMA-β)、胰岛素敏感指数(Insulin sensitivity index,ISI)、定量胰岛素敏感性指数(Quantitative insulin sensitivity check index,QUICKI)等参数。实验结束时,收集血清和胰腺组织进行生化、病理分析。

结果

采用HFD+STZ成功构建了肥胖T2DM动物模型。参苓白术散及其拆分组分能够减轻肥胖T2DM大鼠体质量、减少腹围,缓解肥胖T2DM大鼠多饮、多食的表型,调节脂代谢。能够降低肥胖T2DM大鼠空腹血糖,改善葡萄糖耐量、胰岛素耐量及丙酮酸耐量,改善胰岛形态及功能,调节糖代谢。

结论

参苓白术散及其拆分组分可有效改善肥胖T2DM,调节糖、脂代谢紊乱,修复胰腺的病理损伤。参苓白术散多糖是改善肥胖T2DM的最佳有效部位。参苓白术散多糖组分、树脂70%醇洗组分、水洗组分为参苓白术散“甘”味的主要物质基础,其共同发挥着参苓白术散改善肥胖T2DM的作用。

, authors=杨可威1, 2, 朱连连1, 2, 禹姗姗1, 2, 陈正元3, 吴瑾1, 2, 王爽1, 2, 战丽彬1, 2, authorsList=杨可威, 朱连连, 禹姗姗, 陈正元, 吴瑾, 王爽, 战丽彬, authorCompany=null, correspAuthors=朱连连, 战丽彬, authorNote=

杨可威(1998-),男,辽宁海城人,硕士在读,研究方向:脾脏象理论及其应用的现代研究。

, correspAuthorsNote=
战丽彬(1964-),女,辽宁大连人,教授,博士研究生导师,博士,研究方向:脾脏象理论及其应用的现代研究。E-mail:。
朱连连(1991-),男,辽宁大连人,助理研究员,博士,研究方向:脾脏象理论及其应用的现代研究。E-mail:。
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articleId=1322926110471758625, language=CN, label=图9, caption=各组大鼠胰腺匀浆液耗氧率比较, figureFileSmall=YQ24S0zNHWkDWY28YO32pA==, figureFileBig=qGgh9qyOB6BR4WmWWAYyew==, tableContent=null), ArticleFig(id=1322926117417526148, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926110471758625, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
时间/(min)水(A)/(%)乙腈/(%)
0982
5982
107723
307525
400100
), ArticleFig(id=1322926117501412229, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926110471758625, language=CN, label=表1, caption=

梯度洗脱

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时间/(min)水(A)/(%)乙腈/(%)
0982
5982
107723
307525
400100
), ArticleFig(id=1322926117568521094, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926110471758625, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
样品净重/(g)收率/(%)
VOF0.300 00.07
PF77.414 517.44
WEF65.117 614.67
40%EF3.051 60.69
70%EF1.801 90.41
95%EF0.211 80.05
), ArticleFig(id=1322926117644018567, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926110471758625, language=CN, label=表2, caption=

参苓白术散各拆分组分收率

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样品净重/(g)收率/(%)
VOF0.300 00.07
PF77.414 517.44
WEF65.117 614.67
40%EF3.051 60.69
70%EF1.801 90.41
95%EF0.211 80.05
), ArticleFig(id=1322926117719516040, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926110471758625, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别体质量腹围摄食量饮水量空腹血糖OGTTITTPTTFINSGHbA1CHOMAIRLee’s指数脂体比TGTCLDL-CFFA综合评分
C1.105 41.057 91.151 90.704 40.425 30.407 10.455 40.411 00.926 40.663 60.375 80.990 30.79810.895 00.864 70.759 51.063 40.564 1
M1.098 91.063 21.517 32.345 61.927 91.387 21.382 31.990 21.442 01.406 42.683 21.004 61.205 32.555 91.107 81.437 51.123 51.497 7
L0.936 80.951 20.883 00.914 80.667 10.856 10.749 90.860 80.942 80.758 30.405 70.965 31.072 00.972 71.066 21.003 71.062 40.757 7
SLBZP0.961 40.967 20.741 60.684 80.885 10.942 90.792 30.838 90.962 50.842 50.732 90.991 50.971 70.470 51.016 30.852 21.032 00.804 5
VOF0.977 80.993 20.913 20.811 70.922 91.151 51.151 81.002 30.90990.986 80.783 11.018 41.109 81.023 61.124 41.045 10.933 80.931 2
PF0.963 80.987 90.860 90.757 30.751 61.151 50.897 10.925 30.927 40.944 20.696 40.998 60.990 00.892 91.031 00.846 50.978 00.858 1
WEF0.984 60.993 20.923 61.014 30.999 41.027 40.997 80.958 10.922 60.962 30.849 71.014 11.019 50.538 01.046 90.886 51.021 40.877 8
40%EF0.960 50.981 20.977 21.019 01.181 90.920 81.185 50.966 80.957 81.032 61.301 51.010 31.007 80.910 31.019 11.166 50.961 80.958 3
70%EF1.004 10.987 20.901 00.647 10.937 30.959 31.101 40.941 70.986 61.219 00.781 11.015 00.912 80.751 40.855 50.968 40.914 70.879 0
95%EF1.006 61.017 91.130 41.100 91.301 51.196 21.286 61.104 91.021 91.184 31.390 30.991 70.915 00.989 80.867 91.035 20.908 91.061 6
), ArticleFig(id=1322926117832762249, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926110471758625, language=CN, label=表3, caption=

参苓白术散各拆分组分对肥胖2型糖尿病治疗效果的综合评分(↓)

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组别体质量腹围摄食量饮水量空腹血糖OGTTITTPTTFINSGHbA1CHOMAIRLee’s指数脂体比TGTCLDL-CFFA综合评分
C1.105 41.057 91.151 90.704 40.425 30.407 10.455 40.411 00.926 40.663 60.375 80.990 30.79810.895 00.864 70.759 51.063 40.564 1
M1.098 91.063 21.517 32.345 61.927 91.387 21.382 31.990 21.442 01.406 42.683 21.004 61.205 32.555 91.107 81.437 51.123 51.497 7
L0.936 80.951 20.883 00.914 80.667 10.856 10.749 90.860 80.942 80.758 30.405 70.965 31.072 00.972 71.066 21.003 71.062 40.757 7
SLBZP0.961 40.967 20.741 60.684 80.885 10.942 90.792 30.838 90.962 50.842 50.732 90.991 50.971 70.470 51.016 30.852 21.032 00.804 5
VOF0.977 80.993 20.913 20.811 70.922 91.151 51.151 81.002 30.90990.986 80.783 11.018 41.109 81.023 61.124 41.045 10.933 80.931 2
PF0.963 80.987 90.860 90.757 30.751 61.151 50.897 10.925 30.927 40.944 20.696 40.998 60.990 00.892 91.031 00.846 50.978 00.858 1
WEF0.984 60.993 20.923 61.014 30.999 41.027 40.997 80.958 10.922 60.962 30.849 71.014 11.019 50.538 01.046 90.886 51.021 40.877 8
40%EF0.960 50.981 20.977 21.019 01.181 90.920 81.185 50.966 80.957 81.032 61.301 51.010 31.007 80.910 31.019 11.166 50.961 80.958 3
70%EF1.004 10.987 20.901 00.647 10.937 30.959 31.101 40.941 70.986 61.219 00.781 11.015 00.912 80.751 40.855 50.968 40.914 70.879 0
95%EF1.006 61.017 91.130 41.100 91.301 51.196 21.286 61.104 91.021 91.184 31.390 30.991 70.915 00.989 80.867 91.035 20.908 91.061 6
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组别GLP-1HOMA-βISIQUICKIO2kHDL-C综合评分
C0.999 52.594 11.814 41.307 21.351 40.775 30.096 7
M0.759 20.444 60.298 30.690 30.911 60.525 30.042 1
L1.542 91.964 81.633 41.244 31.190 00.835 40.094 9
SLBZP1.068 40.816 40.995 41.008 80.997 30.707 00.068 4
VOF1.034 70.642 70.944 20.989 01.043 00.704 00.066 6
PF1.068 10.917 21.222 21.093 80.994 11.324 60.103 1
WEF0.839 50.739 40.896 10.968 40.871 81.532 50.104 3
40%EF1.021 80.440 50.632 70.855 00.771 21.260 80.084 9
70%EF0.968 30.819 90.905 30.975 70.988 91.160 40.087 9
95%EF0.697 70.620 30.656 40.867 90.880 51.174 40.081 1
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苓白术散各拆分组分对肥胖2型糖尿病治疗效果的综合评分(↑)

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组别GLP-1HOMA-βISIQUICKIO2kHDL-C综合评分
C0.999 52.594 11.814 41.307 21.351 40.775 30.096 7
M0.759 20.444 60.298 30.690 30.911 60.525 30.042 1
L1.542 91.964 81.633 41.244 31.190 00.835 40.094 9
SLBZP1.068 40.816 40.995 41.008 80.997 30.707 00.068 4
VOF1.034 70.642 70.944 20.989 01.043 00.704 00.066 6
PF1.068 10.917 21.222 21.093 80.994 11.324 60.103 1
WEF0.839 50.739 40.896 10.968 40.871 81.532 50.104 3
40%EF1.021 80.440 50.632 70.855 00.771 21.260 80.084 9
70%EF0.968 30.819 90.905 30.975 70.988 91.160 40.087 9
95%EF0.697 70.620 30.656 40.867 90.880 51.174 40.081 1
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参苓白术散改善肥胖2型糖尿病有效部位的筛选
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杨可威 1, 2 , 朱连连 1, 2 , 禹姗姗 1, 2 , 陈正元 3 , 吴瑾 1, 2 , 王爽 1, 2 , 战丽彬 1, 2
中华中医药学刊 | 国家项目点击 2025,43(7): 182-189
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中华中医药学刊 |国家项目点击 2025 , 43 (7) : 182 -189
参苓白术散改善肥胖2型糖尿病有效部位的筛选
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杨可威1, 2, 朱连连1, 2 , 禹姗姗1, 2, 陈正元3, 吴瑾1, 2, 王爽1, 2, 战丽彬1, 2
作者信息
  • 1.辽宁中医药大学中医脏象理论及应用教育部重点实验室,辽宁 沈阳 110847
  • 2.辽宁中医药大学辽宁省中医脾脏象现代研究重点实验室,辽宁 沈阳 110847
  • 3.南京中医药大学中西医结合学院,江苏 南京 210023
通讯作者:
战丽彬(1964-),女,辽宁大连人,教授,博士研究生导师,博士,研究方向:脾脏象理论及其应用的现代研究。E-mail:。
朱连连(1991-),男,辽宁大连人,助理研究员,博士,研究方向:脾脏象理论及其应用的现代研究。E-mail:。
作者简介:

杨可威(1998-),男,辽宁海城人,硕士在读,研究方向:脾脏象理论及其应用的现代研究。

Screening of Effective Parts of Shenling Baizhu Powder(参苓白术散)for Improving Obese Type 2 Diabetes Mellitus
Kewei YANG1, 2, Lianlian ZHU1, 2 , Shanshan YU1, 2, Zhengyuan CHEN3, Jin WU1, 2, Shuang WANG1, 2, Libin ZHAN1, 2
Affiliations
  • 1.Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China
  • 2.Key Laboratory of Liaoning Province for TCM Spleen-Viscera-State Modern Research,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China
  • 3.School of Integrated Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu,China
出版时间: 2025-07-10 doi: 10.13193/j.issn.1673-7717.2025.07.036
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目的

观察参苓白术散(Shenling Baizhu Powder,SLBZP)及其拆分组分对高脂饮食(High fat diet,HFD)结合小剂量链脲佐菌素(Streptozotocin,STZ)所致肥胖2型糖尿病(Type 2 diabetes mellitus,T2DM)大鼠糖脂代谢的影响,从而获得参苓白术散改善肥胖2型糖尿病的最佳有效部位,并阐明参苓白术散以“甘”治“甘”的主要物质基础。

方法

采用参苓白术散及其拆分组分、利拉鲁肽治疗肥胖T2DM大鼠。定期测量大鼠的体质量、腹围、摄食量、饮水量、空腹血糖,给药结束后进行口服葡萄糖耐量试验(Oral glucose tolerance test,OGTT)、胰岛素耐量试验(Insulin tolerance test,ITT)、丙酮酸耐量试验(Pyruvate tolerance test,PTT)。计算稳态模型-胰岛素抵抗指数(Homeostasis model assessment of insulin resistance index,HOMA-IR)、稳态模型胰岛素分泌指数(Homeostasis model assessment ofβ-cell,HOMA-β)、胰岛素敏感指数(Insulin sensitivity index,ISI)、定量胰岛素敏感性指数(Quantitative insulin sensitivity check index,QUICKI)等参数。实验结束时,收集血清和胰腺组织进行生化、病理分析。

结果

采用HFD+STZ成功构建了肥胖T2DM动物模型。参苓白术散及其拆分组分能够减轻肥胖T2DM大鼠体质量、减少腹围,缓解肥胖T2DM大鼠多饮、多食的表型,调节脂代谢。能够降低肥胖T2DM大鼠空腹血糖,改善葡萄糖耐量、胰岛素耐量及丙酮酸耐量,改善胰岛形态及功能,调节糖代谢。

结论

参苓白术散及其拆分组分可有效改善肥胖T2DM,调节糖、脂代谢紊乱,修复胰腺的病理损伤。参苓白术散多糖是改善肥胖T2DM的最佳有效部位。参苓白术散多糖组分、树脂70%醇洗组分、水洗组分为参苓白术散“甘”味的主要物质基础,其共同发挥着参苓白术散改善肥胖T2DM的作用。

参苓白术散  /  拆分组分  /  肥胖2型糖尿病  /  糖脂代谢
Objective

To observe the effects of Shenling Baizhu Powder(参苓白术散,SLBZP)and its separated components on glucose and lipid metabolism in obese type 2 diabetes mellitus(T2DM)rats induced by high-fat diet(HFD)combined with low-dose streptozotocin(STZ),so as to obtain the best effective part of SLBZP to improve obese T2DM,and to clarify the main material basis of SLBZP to treat T2DM with“sweet drugs”.

Methods

The obese T2DM rats were treated with SLBZP,its split components and liraglutide. The body weight,abdominal circumference,food intake,water intake and fasting blood glucose of rats were measured regularly,and oral glucose tolerance test(OGTT),insulin tolerance test(ITT)and pyruvate tolerance test(PTT)were performed after administration. Homeostasis model assessment of insulin resistance index(HOMA-IR),homeostasis model assessment ofβ-cell(HOMA-β),insulin sensitivity index(ISI),quantitative insulin sensitivity check index(QUICKI)and other parameters were calculated. At the end of the study,the serum and pancreatic tissue were collected for biochemical and pathological analysis.

Results

The obese T2DM animal model was successfully established by HFD+STZ.SLBZP and its split components can reduce the weight and abdominal circumference of obese T2DM rats,alleviate the phenotype of polyphagia and polydipsia in obese T2DM rats,and regulate lipid metabolism. It can reduce fasting blood glucose,improve glucose tolerance,insulin tolerance and pyruvate tolerance,islet morphology and function,and regulate glucose metabolism in obese T2DM rats.

Conclusion

SLBZPand its separated components can effectively improve obese T2DM,regulate the disorder of glucose and lipid metabolism,and repair the pathological damage of pancreas. Polysaccharide of SLBZP is the best effective part to improve obese T2DM. The polysaccharides faction,70% ethanol fraction and water eluted fraction of SLBZPare the main material basis of the“sweet”taste of SLBZP,which together play the role of SLBZPin improving obese T2DM.

Shenling Baizhu Powder(参苓白术散)  /  separated components  /  obese type 2 diabetes mellitus  /  glycolipid metabolism
杨可威, 朱连连, 禹姗姗, 陈正元, 吴瑾, 王爽, 战丽彬. 参苓白术散改善肥胖2型糖尿病有效部位的筛选. 中华中医药学刊, 2025 , 43 (7) : 182 -189 . DOI: 10.13193/j.issn.1673-7717.2025.07.036
Kewei YANG, Lianlian ZHU, Shanshan YU, Zhengyuan CHEN, Jin WU, Shuang WANG, Libin ZHAN. Screening of Effective Parts of Shenling Baizhu Powder(参苓白术散)for Improving Obese Type 2 Diabetes Mellitus[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (7) : 182 -189 . DOI: 10.13193/j.issn.1673-7717.2025.07.036
2型糖尿病(Type 2 diabetes mellitus,T2DM)是一组常见的以胰岛素抵抗和(或)胰岛素分泌障碍为特征的代谢内分泌疾病。2021年,全球共有5.29亿糖尿病患者,其中96.0%为2型糖尿病[1]。T2DM的发生、发展与肥胖密切相关,肥胖T2DM的主要发病机制有胰岛素抵抗和胰岛β细胞受损[2]。强有力的证据一致表明肥胖管理可以延缓糖尿病前期进展为2型糖尿病,并且对2型糖尿病治疗有积极意义[3]。因此,研究肥胖T2DM的发病机制和有效的防治方法具有重要的意义和紧迫性。
经典名方参苓白术散出自宋代《太平惠民和剂局方》,2009年收载入《国家基本药物目录》,现收载于2020版《中华人民共和国药典》(一部)。全方由人参、茯苓、白术、山药、白扁豆、莲子、薏苡仁、砂仁、桔梗、甘草共10味药组成,全方药物以甘味为主(十味八甘),是脾虚夹湿的代表性方剂[4]。且自古便有其对消渴治疗的相关记载如《证治准绳·类方》[5]言:“消渴者尤宜”;《证治汇补·消渴》[6]云:“故参苓白术散为收功神药也”;《杂病广要·消渴》[7]谓:“中消初发……久则参苓白术散”;《幼科发挥·脾所生病》[8]曰:“治脾胃虚弱,饮食不进,多困少气……消渴”等。国医大师周仲瑛在其临证经验糖尿病杂谈部分指出:若津虚不能化气,而致气阴两虚,津气俱伤……脾气虚弱者用参苓白术散[9]。
参苓白术散现代临床常用于治疗消化系统疾病等,近年随着疾病谱的变化,根据异病同治的原则,广泛应用于肥胖2型糖尿病等代谢性疾病,疗效确切[10-11]。基础研究方面,参苓白术散可降低肥胖2型糖尿病患者的体质量[12],通过激活AMPK信号通路改善肥胖型T2DM并促进脂质及葡萄糖代谢,从而缓解糖脂代谢紊乱[13],亦可改善肥胖小鼠肠道微生物失衡[14]。另有研究表明参苓白术散可以有效改善代谢综合征大鼠糖脂代谢障碍、胰岛素抵抗,减轻肝脏脂肪变性和炎性细胞浸润,进而减轻炎症反应[15]。本团队以战丽彬教授“脾阴”学说为指导思想,结合前期工作,通过应用经典名方参苓白术散,其体现了甘淡补脾的滋补脾阴用药规律,具有健脾气、滋脾阴、渗脾湿的功效,共奏升降相因、散收并用、补行兼施之功,尤宜于脾气阴虚夹湿的患者,即滋补脾阴理论应用之基础方[2,16-20]。现代研究发现大多数肥胖T2DM患者对肥甘之品表现出明显偏嗜,故干预肥胖T2DM患者的甘味偏嗜有利于疾病的防治。肥胖T2DM患者表现出的甘味偏嗜[21],乃因过食肥甘困脾生湿,影响精微物质的生成与布散,侧面反映了机体对精微物质的缺乏,而甘味药可健脾助运,故提出以甘味药物为主的参苓白术散防治甘味偏嗜为主所致的肥胖T2DM 的“以甘治甘”的治疗策略,从顺患者所喜亦在其宜[22]。然而,相比于单味药,参苓白术散作为中药复方成分更为复杂,其真正的抗肥胖2型糖尿病药效物质基础,还知之甚少,且尚未见对其有效部位的研究报道[23]。因此,本研究需要对参苓白术散不同组分进行药效筛选,从而获得参苓白术散改善肥胖2型糖尿病的最佳有效部位,并阐明参苓白术散“以甘治甘”的主要物质基础。
对参苓白术散中发挥该作用的有效成分群或有效成分的挖掘与揭示对诠释方剂的配伍变化和应用具有积极意义,但尚缺乏系统研究,故就此方向进一步深入探索参苓白术散改善肥胖T2DM的药效物质基础,以期为参苓白术散的临床应用及研制开发奠定基础。
ZNHW 型智能恒温电热套(巩义市予华仪器有限责任公司);FD5-3T冷冻干燥机(美国西蒙公司);旋转蒸发仪(巩义市予华仪器有限责任公司);XPR105DR十万分之一电子天平(梅特勒托利多);MCA6.6S-2CCN-M百万分之一天平(Sartorius,Germany);Agilent 1290 Infinity超高效液相色谱仪(安捷伦);ACCU-CHE Instant S血糖仪(罗氏);OROBOROS线粒体功能测定系统(奥地利);SpectraMax i3多功能全波长酶标仪(Molecular Devices);TGL-20M台式高速冷冻离心机(湘仪实验仪器有限公司);Chemray 800全自动生化分析仪(深圳雷杜生命科技);M8数字扫描显微成像系统(德国precipoint)等。
参苓白术散药材(人参15 g,茯苓15 g,炒白术15 g,山药15 g,炒白扁豆12 g,莲肉9 g,炒薏苡仁9 g,砂仁6 g,桔梗6 g,炙甘草9 g)均经鉴定符合2020版《中华人民共和国药典》要求,购自于南通三越中药饮片有限公司。无水乙醇(批号:20221025,天津市富宇精细化工有限公司);大孔吸附树脂D-101(批号:20221101,天津市大茂化学试剂厂);甲醇(批号:F22M7L205,美国Fisher Chemical公司);乙腈(批号:204127,美国Fisher Chemical公司);甘草素7,4,-二葡萄糖苷(Glucoliquiritin apioside,批号:121228,成都普菲德生物技术有限公司);人参皂苷Rg2(Ginsenoside Rg2,批号:21062301,成都普菲德生物技术有限公司);芹糖甘草苷(Liquiritin apioside,LOT:F071B206694,上海源叶生物科技有限公司);人参皂苷Rb1(Ginsenoside Rb1,批号:110704-202028,中国食品药品检定研究院);人参皂苷Re(Ginsenoside Re,批号:121107,成都普菲德生物技术有限公司);人参皂苷Rg1(Ginsenoside Rg1,批号:130421,成都普菲德生物技术有限公司);人参皂苷Rf(Ginsenoside Rf,批号:130420,成都普菲德生物技术有限公司);人参皂苷Rb3(Ginsenoside Rb3,批号:121112,成都普菲德生物技术有限公司);人参皂苷Rd(Ginsenoside Rd,批号:131115,成都普菲德生物技术有限公司);人参皂苷Ro(Ginsenoside Ro,批号:130521,成都普菲德生物技术有限公司);小剂量链脲佐菌素(Streptozotocin,STZ)(CAS-No:18883-66-4,美国Sigma公司);柠檬酸钠缓冲溶液(批号:2305001,Solarbio);利拉鲁肽(批号:202206BCF1,诺和力);葡萄糖(批号:20220501,吉林省华牧动物保健品有限公司);胰岛素(批号:22301209,万邦医药);丙酮酸钠(批号:20220325,国药集团化学试剂有限公司);4%多聚甲醛(批号:23179318,biosharp);异氟烷(批号:2023032002,山东安特牧业科技有限公司);大鼠游离脂肪酸(Free fatty acid,FFA)酶联免疫吸附试验检测试剂盒(批号:202310,酶联生物);大鼠胰高血糖素样肽1(Glucagon-like peptide-1,GLP-1)酶联免疫吸附测定试剂盒(批号:Oct 2023,酶联生物);大鼠糖化血红蛋白A1c(Glycosylated hemoglobin A1c,GHbA1c)酶联免疫吸附测定试剂盒(批号:Oct 2023,酶联生物);大鼠空腹胰岛素(Fasting insulin,FINS)酶联免疫吸附测定试剂盒(批号:Oct 2023,酶联生物);酸性乙醇分化液(1%)(批号:2312003,Solarbio)、中性树胶(批号:20231120,Solarbio)、苏木素染液(批号:CR2301055,Servicebio)、伊红染液(水溶)(批号:CR2310011,Servicebio)等。
所有程序均按照辽宁中医药大学机构动物护理和使用委员会指南(伦理批准号:21000042023072)中的建议进行。6周龄SPF级健康雄性SD大鼠,平均体质量(200±20)g,购自辽宁长生生物技术有限公司,许可证编号:SCXK(辽)2020-0001。空白对照组予普通饲料,其余各组予诱导饲料(货号:HF45、Dyets)。饲养于辽宁中医药大学动物实验中心,明暗12 h规律自然光照(12 h∶12 h),温度(21±2)℃,相对湿度60%±10%,自由饮食,饮水。
根据课题组前期方法[24-26]及预实验,具体参苓白术散化学拆分组分制备流程见图1。
精密称取适量的各对照品,加甲醇溶解,定容至容量瓶,制成一定浓度的标准品溶液,过0.22 μm微孔滤膜,即得。
精密称取适量的参苓白术散水煎液和各拆分组分冻干粉,溶解,制成一定浓度的供试品溶液,过0.22μm微孔滤膜,即得。
见表1。Agilent ZORBAX SB-C18柱(150 mm×4.6 mm,5μm),柱温40℃,流速0.3 mL/min,进样量5 μL。采用DAD检测器,光谱:选择“全部”的模式。
适应性饲养1周后,健康雄性SD大鼠90只,随机数字表法选取9只大鼠设为空白对照组(C),普通饲料喂养,而其余大鼠高脂饲料喂养,均自由进食进水。经高脂饲料喂养后获得肥胖大鼠,除空白对照组外所有组按30 mg/kg体质量的剂量一次性快速腹腔注射1% STZ溶液,空白对照组腹腔注射等量柠檬酸钠缓冲液。进行进一步造模,根据随机血糖筛选后获得肥胖T2DM大鼠。肥胖T2DM大鼠(81只)采用随机数字表法分为肥胖T2DM模型组(M)、阳性对照组(利拉鲁肽组,L)、参苓白术散(SLBZP)及其拆分组分组。造模分组后空白对照组继续以普通饲料喂养,其余组仍以高脂饲料喂养。造模成功次日开始灌胃处理,以1 mL/100 g体质量灌胃给药4周,根据课题组前期筛选参苓白术散水煎液最佳有效剂量结果(24 g·kg-1)[17],后续实验将采用此模型研究该剂量下参苓白术散水煎液拆分组分对肥胖T2DM的影响。根据不同拆分组分收率换算成相应倍数生药量;肥胖T2DM模型组和空白对照组同法给予超纯水灌胃4周。
实验结束时,禁食不禁水12 h后将所有动物用异氟烷麻醉,经腹主动脉取血,收集组织,保存至-80℃冰箱内直至检测。
给药期间,每周记录各组大鼠的体质量、腹围、体长、摄食量及饮水量等。
体质量(g)^(1/3)×10/体长(mm),体长定义为鼻到肛门的距离。
脂体比=(肾周脂肪g+睾周脂肪g)/体质量(g)×100%。
给药期间,每周检测空腹血糖(Fasting blood glucose,FBG)。
在治疗的第4周结束时进行口服葡萄糖耐量试验(Oral glucose tolerance test,OGTT)、胰岛素耐量试验(Insulin tolerance test,ITT)、丙酮酸耐量试验(Pyruvate tolerance test,PTT)。OGTT:大鼠禁食12 h后,用50%葡萄糖溶液按2 g/kg体质量灌胃(换算成溶液体积为0.4 mL/100 g体质量灌胃),在服糖前(0 min)、服糖后30、60、90、120 min尾静脉采血测定血糖水平。ITT:OGTT后适应性喂养1 d后,大鼠禁食6 h后,腹腔注射普通短效胰岛素(0.5 U/kg体质量)。于注射前(0 min)及注射后15、30、60、90、120 min尾静脉采血测定血糖水平。PTT:ITT后适应性喂养1 d后,大鼠禁食12 h后,称取体质量,采用腹腔注射的方式,按丙酮酸钠的量为2 g/kg(现用现配2 g/10 mL,10 mL/kg),腹腔注射体积为1 mL/100 g。于注射前(0 min)及注射后30、60、90、120 min尾静脉采血测定血糖水平。
应用酶联免疫吸附法测定大鼠血清中HbA1c、FINS、GLP-1、FFA水平,具体操作严格按照试剂盒说明书进行。
采用全自动生化仪自动测定血清中总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)和高密度脂蛋白胆固醇(High-density lipoprotein cholesterol,HDL-C)水平。
稳态模型-胰岛素抵抗指数(Homeostasis model assessment of insulin resistance index,HOMA-IR)=FBG×FINS/22.5;稳态模型胰岛素分泌指数(Homeostasis model assessment ofβ-cell,HOMA-β)=20×FINS/(FBG-3.5);胰岛素敏感指数(Insulin sensitivity index,ISI)=1/(FBG×FINS);定量胰岛素敏感性指数(Quantitative insulin sensitivity check index,QUICKI)=1/(Log FBG+Log FINS);胰腺组织HE染色。
(1)制备组织匀浆液:①冰上取材后,立刻称量,一般5~10 mg/仓(离体处理要迅速),其余未称量组织置于冰PBS备用;②剪碎;③将细碎组织+1 mL MIR05放入手动玻璃匀浆器中匀浆,至得到无碎块的混悬液即可;④匀浆后过滤较大残渣(若无较大残渣,可忽略过滤),即可得到组织匀浆液。(2)O2k上样量:每仓5~10 mg组织+1 mL MIR05呼吸介质,制备1 mL组织匀浆液。(3)加样并关仓:取下塞子,吸走仓内1 mL BUFFER,用移液器将1 mL组织匀浆液加入到仓室中,即仓内总体积为2 mL,封闭仓室进行检测。滴定方案:G+M+P+ADP(D)+CYTC+SCC(S)+U+ROT+AMA。
数据均采用Prsim 9.0软件作统计分析,数值以均数±标准差表示,多组均数的比较采用单因素方差分析(one-way ANOVA),以P<0.05为差异有统计学意义。
将参苓白术散化学成分拆分成挥发油组分(Volatile oil faction,VOF)、多糖组分(polysaccharides faction,PF)、树脂水洗组分(water eluted fraction,WEF)、树脂40%醇洗组分(40%ethanol fraction,40%EF)、树脂70%醇洗组分(70% ethanol fraction,70%EF)、树脂95%醇洗组分(95% ethanol fraction,95%EF)。参苓白术散各拆分组分收率见表2。遵循化学组分拆分原则,即以中药的理化特性等为依据拆分复方中的全部化学成分,不改变化学成分的化学性质,并且各拆分组分均具有较小的交叉性。采用生药峰面积交叉分析方法[27-28],经计算树脂水洗组分与树脂40%醇洗组分交叉度为0.372 7;树脂40%醇洗组分与树脂70%醇洗组分交叉度为0.063 8;树脂70%醇洗组分与树脂95%醇洗组分交叉度为0.079 4。结合收率以及交叉度分析结果,可知参苓白术散各拆分组分有较好的分离度,工艺成熟。见插页LⅠ图2。
实验期间各组大鼠的体质量、腹围变化如插页LⅡ图3所示。喂食高脂饲料的大鼠的体质量较空白对照组增加,高脂饲料喂养4周后,高脂饲喂大鼠体质量有升高趋势。腹腔注射1%STZ溶液后,M组、L组、SLBZP及其拆分组分组大鼠的体质量下降。给药后,与M组相比各组大鼠体质量有所降低;给药第4周时,L组(P<0.01)、SLBZP组(P<0.05)、PF组(P<0.05)、40%EF组(P<0.05)的大鼠体质量减少更为显著。
高脂饲料喂养4周后,发现高脂饲喂大鼠腹围高于C组;给药后,相比于M组各给药组大鼠腹围有降低的趋势。给药第4周时,L组(P<0.001)、SLBZP组(P<0.01)、PF组(P<0.05)、40%EF组(P<0.05)、70%EF组(P<0.05)的大鼠腹围减少更为显著。
与C组相比,M组的Lee’s指数有升高的趋势,给药后有降低的趋势,而无统计学意义(P>0.05);与C组相比,M组的脂体比显著升高(P<0.05),给药后有降低的趋势。
实验中各组大鼠的摄食量和饮水量变化如插页LⅡ图4所示。在肥胖阶段的摄食过程中,前3周喂食高脂饲料的大鼠进食量较喂食普通饲料的C组大鼠减少,在第4周摄食量高于C组。腹腔注射1%STZ溶液后,给药前M组及各给药组大鼠摄食量有所降低。M组在没有药物治疗的情况下,进食量较C组有所增加。给药1周后,M组及各给药组大鼠摄食量有所回升。在给药第2周开始,各给药组的进食量较M组有所减少。
根据饮水量结果可知,在喂养前4周,C组的饮水量在刚开始较喂养高脂饲料的大鼠有增加的趋势,而后两周喂养高脂饲料的大鼠饮水量较C组有增加的趋势。在第4周后腹腔注射1%STZ溶液后,M组、L组、SLBZP及其拆分组分组大鼠的饮水量较C组升高,表现出明显的T2DM多饮的特征。与M组大鼠相比,L组、SLBZP及拆分组分组大鼠的饮水量显著下降,L组、SLBZP组、VOF组、PF组、70%EF组疗效更为显著。
与C组相比,注射1%STZ溶液的T2DM大鼠FBG显著升高。T2DM大鼠的FBG显示,所有大鼠FBG均大于11.1 mmol/L,T2DM成模率良好。随着给药,与M组相比,给药组显著降低肥胖T2DM大鼠FBG,其中L组、PF组、SLBZP组、VOF组、70%EF组治疗可显著降低FBG。
本研究比较了实验结束时各组大鼠FINS、GHbA1c及GLP-1的表达情况,结果可见,给药结束后,与C组相比,M组的大鼠空腹胰岛素明显增加(P<0.000 1),与M组相比,各给药组FINS明显降低,与M组相比差异均具有统计学意义(P<0.05)。
给药1周后OGTT、ITT,与C组相比,肥胖T2DM大鼠在一定程度上出现糖调节受损,葡萄糖耐量、胰岛素耐量出现异常。在各给药干预1周后,T2DM大鼠的葡萄糖耐量受损和胰岛素不耐受状况尚未得到显著改善。在给药结束后,T2DM大鼠的葡萄糖耐量、胰岛素耐量及丙酮酸耐量状况得到改善。见插页LⅢ图5。
与C组比较,M组大鼠血清中TC、TG、LDL-C、FFA含量升高,HDL-C含量则降低。给药结束后,与M组比较,各给药组降低了TC、TG、LDL-C及FFA水平,并提高了HDL-C水平。肥胖T2DM大鼠的TC、TG、LDL-C情况获得了改善,VOF组、PF组及醇洗组分组显著降低了大鼠血清中FFA的含量(P<0.05,P<0.01,P<0.001,P<0.000 1),PF组、WEF组、醇洗组分组显著增加了大鼠血清中HDL-C的含量(P<0.000 1)。这些结果表明,SLBZP及其拆分组分可以改善肥胖T2DM大鼠脂质代谢。见插页LⅣ图6。
与C组相比,M组大鼠HOMA-IR明显高于C组(P<0.000 1),说明建立的肥胖T2DM大鼠模型出现了胰岛素抵抗症状。药物干预结束后,各给药组HOMA-IR下降明显,与M组相比差异均具有统计学意义(P<0.01,P<0.001,P<0.000 1)。与C组相比,M组大鼠HOMA-β指数显著降低(P<0.000 1),给药干预结束后,各给药组胰岛β细胞功能指数有升高的趋势,L组较M组HOMA-β显著升高(P<0.001)。与C组相比,M组大鼠ISI显著降低(P<0.000 1),药物干预结束后,各给药组ISI显著升高(P<0.01,P<0.001,P<0.000 1)。M组QUICKI值较C组明显降低(P<0.000 1),药物干预结束后,QUICKI值显著升高(P<0.01,P<0.001,P<0.000 1),说明参苓白术散及其拆分组分能够显著改善胰岛素抵抗大鼠的胰岛素敏感性。见插页LⅣ图7。
胰岛形态学变化如插页LⅤ图8所示,C组大鼠胰岛形态正常,呈椭圆形,胰岛细胞排列紧密,细胞核大小基本一致。M组大鼠胰岛形态破坏严重,呈不规则形状,边缘不整,胰岛细胞排列不均,细胞核形态改变。SLBZP及其拆分组分组大鼠胰岛形态大体完整,多呈椭圆形,边界较为清楚,少数细胞核代偿性增大,较M组改善明显。L组大鼠胰岛形态基本完整,细胞排列相对均匀,细胞核可见代偿性增大,未见明显损伤。
与C组相比,M组胰腺匀浆液耗氧率降低;与M组相比,L组、SLBZP组、PF组、VOF组、70%EF组胰腺匀浆液耗氧率均有升高的趋势,提示参苓白术散及其拆分组分在肥胖T2DM的胰腺功能障碍和损伤中发挥重要作用。见插页LⅥ图9。
通过研究文献中参苓白术散治疗肥胖2型糖尿病的相关指标,确定参苓白术散治疗肥胖2型糖尿病的评价指标中各指标的重要程度[29]。根据均值化法[30],对参苓白术散各拆分组分的不同指标数据进行归一化处理(表3、表4),公式为:
研究结果表明参苓白术散及其拆分组分能够下调体质量、腹围、摄食量、饮水量、空腹血糖、OGTT、ITT、PTT、FINS、GHbA1C、HOMA-IR、Lee’s指数、脂体比、TG、TC、LDL-C、FFA,由表3结果可知,参苓白术散多糖组分和水洗组分综合评分最高,其次是树脂70%醇洗组分;研究结果表明参苓白术散及其拆分组分能够上调GLP-1、HOMA-β、ISI、QUICKI、胰腺匀浆液耗氧率、HDL-C,由表4结果可知,参苓白术散水洗组分和多糖组分综合评分最高,其次是70%醇洗组分。综上,参苓白术散多糖是改善肥胖T2DM的最佳有效组分,参苓白术散多糖组分、树脂70%醇洗组分、水洗组分是参苓白术散中改善肥胖T2DM的主要物质基础。
既往的实验研究证实,参苓白术散能够改善肥胖T2DM;但是该组方发挥作用的部位尚不明确,因而,在此次研究中,采用科学的提取分离方法制备参苓白术散不同拆分组分,以改善肥胖T2DM作用作为评价指标,通过观察大鼠一般状态,进行药效筛选,明确该方改善肥胖T2DM的有效部位。
随着中药及复方的不断开发利用,中药及复方的药理活性及活性部位的筛选与研究受到人们的关注。中药多采用水提取,若要进行药效物质研究,首先需要对这“一锅汤”进行组分拆分,并对拆分组分进行差异度的科学分析研究[27]。参苓白术散源自宋《太平惠民合剂局方》:人参15 g,茯苓15 g,炒白术15 g,山药15 g,莲子9 g,炒薏苡仁9 g,炒白扁豆12 g,砂仁6 g,桔梗6 g,炙甘草9 g。根据文献报道,一般认为皂苷类和多糖类等是人参的有效物质基础[31];倍半萜类和三萜类等是白术的有效物质基础[32];三萜类等是茯苓的有效物质基础[33];皂苷类、多糖类、黄酮类和山药素类是山药的有效物质基础[34];生物碱类、黄酮类是莲子的有效物质基础[35];多糖类、皂苷类、氨基酸等是白扁豆的有效物质基础[36];脂肪酸及其脂类是薏苡仁的有效物质基础[37];挥发油类是砂仁的有效物质基础[38];皂苷类和黄酮类是桔梗的有效物质基础[39];三萜皂苷类和黄酮类是甘草的有效物质基础[40]。因此,本研究遵循化学组分拆分原则,以中药的理化特性等为根据拆分复方。利用水蒸气蒸馏法与水提醇沉法,通过大孔吸附树脂柱色谱法,对参苓白术散化学组分进行拆分,并通过超高效液相色谱法对各拆分组分进行表征。旨在对参苓白术散化学组分拆分进行研究,并分别利用定性分析与半定量分析从组分间的不交叉性角度研究参苓白术散化学拆分组分的不交叉性的程度,为进一步评价各拆分组分的药效物质基础提供科学依据。本研究将参苓白术散化学成分拆分成挥发油组分、多糖组分、树脂水洗组分、树脂40%醇洗组分、树脂70%醇洗组分、树脂95%醇洗组分。由于多糖、挥发油组分与小分子部分交叉度很小,因此本研究仅对小分子的树脂水洗组分和树脂醇洗组分进行不交叉性分析。通过对参苓白术散各拆分组分所含化学成分交叉度的考察,各组交叉度较小,各成分得到了较好分离,可作为代表性组分用于后续物质基础研究。
采用HFD+STZ成功构建了肥胖T2DM动物模型。高脂高糖饮食阶段,饲喂高脂高糖饲料的大鼠体质量较空白对照组显著增加,以“高脂高糖饲养大鼠体质量≥空白对照组大鼠体质量20%”为标准筛选肥胖大鼠。腹腔注射STZ后,模型大鼠消瘦,摄食量饮水量增加,尿量增多,为典型T2DM三多一少的症状。同时被毛枯槁、毛色发黄,与C组大鼠有明显不同,此外,成模大鼠3次随机血糖都高于16.7 mmol/L,以上均提示肥胖T2DM大鼠造模成功。研究结果表明,参苓白术散及其拆分组分能够减轻肥胖T2DM 大鼠体质量、减少腹围,缓解肥胖T2DM大鼠多食、多饮的表现,调节脂代谢;能够降低肥胖T2DM大鼠空腹血糖,改善葡萄糖耐量、胰岛素耐量及丙酮酸耐量,改善胰岛形态及功能,调节糖代谢。多指标综合评价分析结果表明,参苓白术散多糖组分和水洗组分综合评分最高,其次是树脂70%醇洗组分,而挥发油组分、树脂40%醇洗组分、树脂95%醇洗组分的有效作用较弱,参苓白术散多糖组分、树脂70%醇洗组分、水洗组分是参苓白术散中改善肥胖T2DM的主要物质基础。然而,有效部位的具体化学成分及其作用机制有待于进一步研究。
多糖由多个单糖单元通过糖苷键连接而成,是自然界最丰富、最重要的生物聚合物之一。自1969年《Nature》杂志首次报道香菇多糖的抗肿瘤作用以来,多糖作为药物的研究和应用引起了国内外学者的广泛关注。中药多糖在免疫调节、抗肿瘤、抗糖尿病、抗氧化、抗病毒、心血管保护和神经保护活性等方面具有突出的药理活性,是近年来中药活性成分研究领域的热点。与单味药多糖相比,复方多糖可结合各单味药多糖的生物活性,起到协同增效的作用[41]。参苓白术散中多糖含量与药效存在着相关性,去除多糖的参苓白术散药效降低,多糖对于主药吸收、转化可能具有重要的催化作用[42]。舒青龙团队研究发现拟杆菌体外利用参苓白术散多糖具竞争优势,中药多糖可作为竞争性碳源调节肠道菌群[43-45]。“拟杆菌/厚壁菌”产丁酸菌组合有利于对中药多糖的降解利用和丁酸生产[46]。根据以参苓白术散多糖为唯一碳源的体外实验提示参苓白术散调节肠道产丁酸菌菌群的机制可能是参苓白术散多糖成分被肠道多糖降解菌先降解为单糖/丙酮酸,再由产丁酸菌将单糖/丙酮酸分解代谢成丁酸,调节肠道菌群与肠道丁酸浓度,达到治疗效果[47]。另外,舒青龙团队研究发现参苓白术散多糖是调节脾气虚证大鼠肠道菌群最重要的活性成分。有研究发现参苓白术散多糖可以改善结肠炎[48]、缓解腹泻[49]。参苓白术散由人参、茯苓、白术等10味药组成,其中人参多糖、茯苓多糖、白术多糖、山药多糖、白扁豆多糖、莲子多糖、薏苡仁多糖、桔梗多糖及甘草多糖均具有降血糖的作用[50-58]。因此,参苓白术散多糖是改善肥胖T2DM的最佳有效部位。
葡萄糖苷酶抑制剂是目前国内广泛应用的一种口服降糖药物,目前有阿卡波糖、伏格列波糖两种,最常使用的是阿卡波糖。阿卡波糖可抑制小肠壁细胞的糖苷酶活性,从而延长对寡糖、双糖和多糖的降解,延缓葡萄糖和果糖的吸收,具有降低餐后血糖和血浆胰岛素浓度的作用。本研究推测参苓白术散水洗组分含有葡萄糖苷酶抑制剂类似作用的化学成分,能够有效改善肥胖T2DM。另外,可能体内的肠道中没有水解“参苓白术散水洗组分”(即某种糖)的酶解系统,因此,它们不被消化吸收,而直接进入肠道内为肠道菌群所利用。所以,糖尿病人食用它们是不影响血糖的。而且,具有此类的功能性低聚糖,由于不影响血糖,同时具有甜味和一定的保健功能,今后可成为糖尿病患者的优选甜味添加剂。树脂醇洗组分中含有大量皂苷。大量研究表明,中药皂苷在降糖[59-60]以及抗肥胖[61-62]方面效果显著。
据报道长期补充膳食纤维会影响大鼠的体质量和某些代谢参数,本研究发现参苓白术散多糖是改善肥胖T2DM的最佳有效部位,这一结果与膳食纤维对一些胃肠疾病有影响作用,能够防止肥胖和改善血糖控制的假设相一致[63]。参苓白术散全方由人参、茯苓、白术、山药、白扁豆、莲子、薏苡仁、砂仁、桔梗、甘草共10味药组成,均为药食同源的物质。上述研究结果让我们看到了参苓白术散多糖对于肥胖T2DM的帮助,既突显出参苓白术散和参苓白术散多糖并用的可能性,也透露出参苓白术散和参苓白术散多糖在个别应用时的实力差距。提供糖尿病患者在药物治疗之外,以食疗稳定血糖的另类思考。提示参苓白术散多糖可作为新型抗肥胖T2DM药物和营养制剂的来源,改善肥胖T2DM状态。参苓白术散多糖作为具有一定开发潜力和研究价值的天然降糖物质,在糖尿病治疗中的应用具有广泛前景。
  • 国家自然科学基金面上项目(82274377)
  • 国家自然科学基金青年科学基金项目(82305066)
  • 中华中医药学会青年人才托举工程项目(2024-QNRC2-B15)
  • 辽宁省科技厅博士科研启动基金计划项目(2023-BS-143)
  • 辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金项目(zyzx2203)
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2025年第43卷第7期
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doi: 10.13193/j.issn.1673-7717.2025.07.036
  • 首发时间:2026-10-30
  • 出版时间:2025-07-10
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基金
国家自然科学基金面上项目(82274377)
国家自然科学基金青年科学基金项目(82305066)
中华中医药学会青年人才托举工程项目(2024-QNRC2-B15)
辽宁省科技厅博士科研启动基金计划项目(2023-BS-143)
辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金项目(zyzx2203)
作者信息
    1.辽宁中医药大学中医脏象理论及应用教育部重点实验室,辽宁 沈阳 110847
    2.辽宁中医药大学辽宁省中医脾脏象现代研究重点实验室,辽宁 沈阳 110847
    3.南京中医药大学中西医结合学院,江苏 南京 210023

通讯作者:

战丽彬(1964-),女,辽宁大连人,教授,博士研究生导师,博士,研究方向:脾脏象理论及其应用的现代研究。E-mail:。
朱连连(1991-),男,辽宁大连人,助理研究员,博士,研究方向:脾脏象理论及其应用的现代研究。E-mail:。
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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2025.07.036
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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
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