基于网络药理学和实验验证探讨知母盐制后治疗糖尿病认知障碍的增效机制  

Exploration on efficiency enhancing mechanism of salt-processing Anemarrhenae Rhizoma in treating diabetes cognitive impairment based on network pharmacology and experimental validation

作　　者：田书青 王晓婷[1,2,3,4] 裴琳秀 王雅竹 高慧 TIAN Shuqing;WANG Xiaoting;PEI Linxiu;WANG Yazhu;GAO Hui(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116600,China;Traditional Chinese Medicine Processing Technology Inheritance Base(Liaoning)of the National Administration of Traditional Chinese Medicine,Dalian 116600,China;Technology Innovation Center for Traditional Chinese Medicine Processing of Liaoning Province,Dalian 116600,China;The First Clinical College,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600 [2]国家中医药管理局中药炮制技术传承基地(辽宁),辽宁大连116600 [3]辽宁省中药炮制专业技术创新中心,辽宁大连116600 [4]辽宁中医药大学第一临床学院,辽宁沈阳110847

出　　处：《中草药》2025年第5期1640-1651,共12页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81102810);国家中医药管理局特色炮制技术规律挖掘项目(GZY-KJS-2022-049)。

摘　　要：目的基于网络药理学和实验验证探讨知母Anemarrhenae Rhizoma盐制后治疗糖尿病认知障碍(diabetes cognitive impairment,DCI)的增效机制,为阐释盐知母炮制增效的科学内涵、临床合理用药提供科学依据。方法中药系统药理学数据库分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)联合课题组前期化学成分分析研究结果获得知母中主要活性成分,采用Swiss Target Prediction数据库预测成分的潜在靶点,从人类基因数据库(Gene cards)和在线人类孟德尔遗传数据库(online Mendelian Inheritance in man,OMIM)的Genemap获得2型糖尿病(type 2 diabetes mellitus,T2DM)和阿尔茨海默病(Alzheimer's disease,AD)疾病的相关靶点,利用Venny数据库获取成分与疾病的交集靶点,并通过STRING数据库和Cytoscape 3.8.2软件分析并构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络。借助Metascape平台进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,利用Cytoscape3.8.2构建“成分-靶点-通路”网络。采用高糖高脂饲料联合链脲佐菌素(streptozotocin,STZ)诱导糖尿病大鼠模型,造模成功后,随机选取48只分为模型组、生知母皂苷组(176.4 mg/kg)、盐知母皂苷组(176.4 mg/kg)、生知母组(2.52 g/kg)、盐知母组(2.52 g/kg)和吡拉西坦(500 mg/kg)组,每组8只,另取8只生理状态大鼠作为对照组,除对照组外,其余各给药组每日上午ig三氯化铝(aluminum chloride,AlCl3,500 mg/kg),构建糖尿病认知障碍(diabetes cognitive impairment,DCI)模型,各给药组每日下午ig给药(10 mL/kg),对照组、模型组ig等体积蒸馏水,1次/d,连续4周。观察各组大鼠毛发的变化情况、测定大鼠体质量和血糖;采用Morris水迷宫法检测大鼠的认知能力;采用苏木素-伊红(hematoxylin eosin,HE)染色观察脑组织海马区病理变化;采用ELISA法检测Objective To explore the efficiency enhancing mechanism of salt-processing Anemarrhenae Rhizoma in the treatment of diabetes cognitive impairment(DCI)based on network pharmacology and experimental validation,providing a scientific basis for elucidating the scientific connotation of the synergy of salt-processing Anemarrhenae Rhizoma and the rational clinical use of drugs.Methods The main active components of Anemarrhenae Rhizoma were obtained by the preliminary chemical composition analysis research results of our research group combined with the traditional Chinese medicine systematic pharmacology database platform(TCMSP),and the potential targets of components were predicted by the Swiss Target Prediction database.The related targets of type 2 diabetes mellitus(T2DM)and Alzheimer’s diseases(AD)were obtained from Ggenemap of the human gene database(Gene cards)and the online Mendelian inheritance in man database(OMIM),and the intersection targets of components and diseases were obtained by Venny database.The protein-protein interaction(PPI)network was analyzed and constructed through the STRNG database and Cytoscape 3.8.2 software.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed by Metascape platform.Cytoscape 3.8.2 was used to construct an“ingredients-targets-pathway”network.In this study,a diabetic rat model was established through a high-fat,high-sugar diet combined with streptozotocin(STZ)induction.After successful modeling,a total of 48 diabetic rats were randomly assigned to the following groups:model group,timosaponins of Anemarrhenae Rhizoma group(176.4 mg/kg),timosaponins of salt-processed Anemarrhenae rhizoma group(176.4 mg/kg),Anemarrhenae Rhizoma group(2.52 g/kg),salt-processed Anemarrhenae Rhizoma group(2.52 g/kg)and piracetam(500 mg/kg)group,with eight rats in each group.Another eight normal rats were taken as the control group.Except for the control group,all treatment groups received 500 mg/kg of AlCl3 via intragastric admi

关 键 词：知母 炮制 总皂苷 糖尿病认知障碍 网络药理学 JNK/TNF-α通路 

分 类 号：R285.5[医药卫生—中药学]