基于中药网络与靶点网络探究中药治疗糖尿病合并缺血性中风的用药规律与作用机制  

Exploration of Rule and Mechanism of Traditional Chinese Medicine in the Treatment of Diabetes with Ischemic Stroke Based on Chinese Herbal Network and Target Network

作　　者：李清丽 李浩 谢雁鸣[1] 刘毅 LI Qingli;LI Hao;XIE Yanming;LIU Yi(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China)

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京100700 [2]中国中医科学院望京医院,北京100102

出　　处：《中国中医基础医学杂志》2024年第4期659-666,共8页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家中医药管理局2021岐黄学者支持项目(国家中医药人教函〔2022〕6);谢雁鸣全国名老中医药专家传承工作室建设项目(国家中医药人教函〔2022〕75)。

摘　　要：目的基于文献来源医案构建中药网络分析治疗糖尿病(diabetes mellitus,DM)合并缺血性中风(ischemic stroke,IS)的中药组方配伍规律,并基于靶点网络分析核心组方的作用机制。方法以中国知网、维普、万方数据库、中国生物医学文献服务系统为文献来源,借助古今医案云平台对文献中的处方进行数据统计以及关联规则、复杂网络和聚类分析,得到核心组方,分析治疗DM合并IS的中药组方规律;从TCMSP数据库检索药物成分以及相应的靶点,从OMIM、TTD、GeneCards数据库中检索DM和IS的靶点,通过Cytoscape 3.9.1软件及MCODE插件得到核心组方有效成分及关键靶点;随后进行靶点基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析;最后通过分子对接技术进行验证。结果纳入文献144篇,处方239首,涉及中药194味,其中黄芪的使用频次最高(103次);关联规则分析得到药物组合6组;得到的核心组方由9味中药组成;核心组方有效成分有槲皮素、水蛭素A、二氢辣椒素、花生四烯酸等;关键靶点包括丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)3、转录因子JUN(transcription factor Jun,JUN)、细胞肿瘤抗原p53(tumor protein P53,TP53)、信号转导和转录激活因子(signal transducer and activator of transcription,STAT)3、SRC原癌基因(SRC proto-oncogene,SRC)、蛋白激酶B(protein kinase B,又称AKT)1、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)1、HRAS原癌基因(HRAS proto-oncogene,HRAS)、凝血酶原F2(coagulation factor Ⅱ,F2)等;GO和KEGG分析显示核心组方治疗DM合并IS与癌症通路、晚期糖基化终末产物-晚期糖基化终末产物受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路、磷脂酰肌醇3激酶(phosphatidylinositol-3-kinase,PI3K)/AKT信号通路、环腺苷酸(cyclic adenosine monophosphate,cAMP)等信Objective Based on the literature sources of medical cases,this study aimed to construct a network analysis of traditional Chinese medicine(TCM)for the treatment of diabetes mellitus(DM)with ischemic stroke(IS),and to explore the compatibility rules of TCM prescriptions.Furthermore,the study aimed to analyze the mechanism of action of the core TCM prescriptions based on target network analysis.Methods CNKI,VIP,Wanfang Database and China Biomedical Literature Service System,were used as the literature sources.Data statistics,association rule analysis,complex network analysis,and cluster analysis of Prescriptions in Literatures Based on Ancient and Modern Medical Case Cloud Platform,then get the core prescription.Analyze the composition rules of TCM.The TCM ingredients and corresponding targets were retrieved from the TCM Systems Pharmacology Database(TCMSP),while the targets related to DM and IS were obtained from the OMIM,TTD,and GeneCards databases.The core ingredients and key targets of the core TCM prescriptions were obtained using Cytoscape 3.9.1 software and the MCODE plugin.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted,followed by molecular docking validation.Results A total of 144 articles and 239 prescriptions were included,involving 194 TCM herbs.Astragalus membranaceus was the most frequently used herb(103 occurrences).Association rule analysis identified six combinations of herbs.The core TCM prescriptions consisted of nine herbs.The effective ingredients of the core TCM prescriptions included quercetin,hirudinoidine A,dihydrocapsaicin,arachidonicacid,etc.Key targets include mitogen-activated protein kinase 3(MAPK3),transcription factor JUN(JUN),tumor protein P53(TP53),signal transducer and activator of transcription 3(STAT3),SRC proto-oncogene(SRC),protein kinase B1(AKT1),mitogen-activated protein kinase 1(MAPK1),HRAS proto-oncogene(HRAS),coagulation factorⅡ(F2)and so on.GO and KEGG analysis showed that the treatment of DM with IS was related to

关 键 词：糖尿病合并缺血性中风 中药网络 靶点网络 补阳还五汤 作用机制 

分 类 号：R285[医药卫生—中药学]