中药组方治疗糖尿病合并骨质疏松症用药规律挖掘及其作用机制的网络药理学与分子对接研究  

Study on Medication Rule of Traditional Chinese Medicine in Treatment of Diabetes with Osteoporosis and lts Mechanism of Action:Network Phamacology and Molecular Docking

作　　者：代俊泽 刘毅 廖翠平 严正 代金刚[3] 谢雁鸣[2] 王朝鲁[1] DAI Junze;LIU Yi;LIAO Cuiping;YAN Zheng;DAI Jingang;XIE Yanming;WANG Chaolu(Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China;Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院望京医院,北京100102 [2]中国中医科学院中医临床基础医学研究所,北京100700 [3]中国中医科学院医学实验中心,北京100700

出　　处：《中华中医药学刊》2024年第12期158-163,I0055-I0057,共9页Chinese Archives of Traditional Chinese Medicine

基　　金：国家中医药传承创新团队项目(ZYYCXTD-C-202003);国家中医药管理局全国名老中医专家传承工作室建设项目(国中医药人教函〔2022〕6号);中国中医科学院医学实验中心协同创新团队项目(XTCX2021004);中国中医科学院望京医院中医药临床循证研究专项(WJYY-XZKT-2023-142)。

摘　　要：目的通过数据挖掘、网络药理学与分子对接分析中医治疗糖尿病(Diabetes Mellitus,DM)合并骨质疏松症(Osteoporosis,OP)的用药规律及作用机制。方法检索中国知网、维普期刊数据库、万方数据库、中国生物医学文献服务系统、pubmed、web of science等数据库收录的相关文献,并利用古今医案云平台构建中医药处方数据库,通过药物频次频率、性味归经、关联规则及系统聚类分析等方式挖掘核心药物;运用中药系统药理学数据库与分析平台(Traditional Chi-nese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索高频药对化合物及治疗靶点,与Genecards和OMIM数据库筛选出糖尿病合并骨质疏松的靶点相映射并取交集;利用STRING 11.0数据库与Cytoscape软件构建可视化蛋白质相互作用网络(Protein-Protein Interaction,PPI)网络与药物成分靶点网络,并对关键靶点进行基因本体论分析(Gene Ontology,GO)和京都基因与基因组百科全书通路富集分析(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,最后进行分子对接。结果共纳入处方108首,涉及药物173味,归经以肝肾脾较为突出,性味以甘苦为主。关联规则分析得到药物组合10组,共7味中药,使用频次在25以上的中药有9味,其中熟地的使用频次最高;关联规则表明药对,山药-熟地,淫羊藿-黄芪支持度最高;聚类分析得到4类中药分类。将关联分析与聚类分析结果与临床应用相结合,最终得到核心组方:“熟地、山药、山茱萸、骨碎补、淫羊藿、黄芪、丹参”。核心药物组合治疗糖尿病合并骨质疏松的关键成分为豆甾醇(Stigmasterol)、亚油酸乙酯(Mandenol)、8-异戊二烯黄酮[8-(3-methylbut-2-enyl)-2-phenyl-chromone],等,核心靶点为IL-6、PPARG、IL1B、VEGFA、NR3C1等,主要通路为AMPK信号通路、cGMP-PKG信号通路等。结论中医药治疗糖尿病合并骨质疏松基本思路为补益肝脾肾三脏,活血Objective To analyze the regularity and mechanism of traditional Chinese medicine(TCM)treating diabetes melli-tus(DM)complicated with osteoporosis(OP)by data mining and network pharmacology.Methods The Chinese medicine pre-scription database was constructed by searching the relevant literature collected from China National Knowledge Infrastructure(CNKI),VIP Chinese Medical Journal Database,Wanfang Database,China Biomedical Literature Service System,PubMed,web of science and so on.The core drugs were mined by means of drug frequency,channel tropism,association rules and systematic cluster analysis.The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to search the compounds and therapeutic targets of high-frequency drugs and the targets were mapped and intersected with Gene-cards and OMIM databases.A visual Protein-Protein Interaction(PPI)network and drug-component-target network were constructed by using STRING 11.0 database and Cytoscape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for key targets.Results A total of 108 prescriptions,involving 173 drugs.The meridian tropism was liver,kidney and spleen meridians.The taste was mainly sweet and bitter.The association rules analysis obtained 10 drug combinations,a total of 7 kinds of Chinese drugs.There were 9 kinds of Chinese drugs were used more than 25 times,and the most frequently used drug was Shudihuang(Rehmanniae Radix Praeparata).Association rules indicated the support degree of Shanyao(Dioscoreae Rhizoma)-Shudihuang(Rehmanniae Radix Praeparata)and Yinhuanghuo(Epimedii Folium)-Huangqi(Astragali Radix)was the highest.The classification of 4 kinds of Chinese drugs was obtained by cluster a-nalysis.Combining the results of association analysis and cluster analysis with clinical application,the core formula was finally obtained:“Shudihuang(Rehmanniae Radix Praeparata),Shanyao(Dioscoreae Rhizoma),Shanzhuyu(Corni Fructus),Gusuibu(Drynariae Rhizo

关 键 词：糖尿病 骨质疏松 中药组方 数据挖掘 网络药理学 作用机制 

分 类 号：R274[医药卫生—中医骨伤科学]