基于网络药理学及分子对接技术探究复方雷公藤逐痛颗粒干预类风湿关节炎的作用机制  

Study on the mechanism of Compound Tripterygium Wilfordii Painkiller Granules on rheumatoid arthritis based on network pharmacology and molecular docking

作　　者：姜平 戴洁梅 魏凯[1,2] 金晔华 常岑 许林帅 时一鸣 何东仪 JIANG Ping;DAI Jiemei;WEI Kai;JIN Yehua;CHANG Cen;XU Linshuai;SHI Yiming;HE Dongyi(Guanghua Clinical Medical College,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Rheumatology,Shanghai Guanghua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200052,China)

机构地区：[1]上海中医药大学光华临床医学院,上海201203 [2]上海中医药大学附属光华医院风湿科,上海200052

出　　处：《上海中医药杂志》2022年第9期21-31,共11页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81774114,82074234);上海市卫健委中西医临床协作试点项目(ZY[2018-2020]-FWTX-1010);上海市卫健委中医专科联盟建设项目(ZY[2018-2020]-FWTX-4017);上海中医药大学“研究生创新培养专项”(Y2021076)

摘　　要：目的运用网络药理学及分子对接技术探究复方雷公藤逐痛颗粒(CTWPGs)干预类风湿关节炎(RA)的分子作用机制。方法通过检索相关文献,并运用中药系统药理学数据库与分析平台(TCMSP)、中医药百科全书数据库(ETCM)、分子机制生物信息学分析工具(BATMAN)等获取CTWPGs的主要活性成分和作用靶点,利用在线人类孟德尔遗传数据库(OMIM)、药物银行(Drug Bank)、基因卡(Gene Cards)、治疗靶点数据库(TTD)等获取RA相关靶点;药物与疾病靶点映射后获取交集靶点,以String数据库对交集靶点构建蛋白互相作用网络,并分析、筛选核心靶点;通过注释、可视化、集成发现数据库(DAVID)对核心靶点进行基因本体论(GO)功能富集分析,以及京都基因和基因组百科全书(KEGG)信号通路分析,采用Cytoscape3.6.0构建CTWPGs“活性成分-靶点-信号通路”的可视化网络。结果通过筛选获得CTWPGs干预RA的作用成分共47种,得到作用于RA的核心靶点34个。GO功能富集分析共得到357个条目(P<0.05),其中生物过程条目299个,细胞组成条目21个,分子功能条目37个;KEGG通路分析富集得到107条信号通路(P<0.05),主要包括肿瘤坏死因子(TNF)信号通路、Toll样受体信号通路和丝裂原活化蛋白激酶(MAPK)信号通路等。最终“活性成分-靶点-信号通路”蛋白互作网络分析结果显示,CTWPGs活性成分中发挥干预RA作用的关键成分为槲皮素、木犀草素、雷公藤甲素等;关键靶点为环加氧酶2(PTGS2)、肉瘤病毒17癌基因同源物(JUN)、丝氨酸/苏氨酸激酶1(AKT1)、丝裂原活化蛋白激酶1(MAPK1)、网状内皮增生症病毒癌基因同源物A(RELA)、丝裂原活化蛋白激酶14(MAPK14)、丝裂原活化蛋白激酶3(MAPK3)、TNF等。分子对接结果显示,木犀草素与MAPK3、PTGS2,雷公藤甲素与MAPK3、TNF,山柰酚与MAPK14,银杏内酯A30与MAPK3、TNF、AKT1、PTGS2,黄芩素与MAPK3之间具有较好的对接活性。结论基于Objective The study used a network pharmacology approach and molecular docking technology to identify the pharmacological mechanisms of Compound Tripterygium Wilfordii Painkiller Granules(CTWPGs)treating rheumatoid arthritis(RA).Methods The main active ingredients and targets of CTWPGs were obtained by using TCMSP,ETCM and BATMAN.RA-related targets were obtained from OMIM,Drug Bank,Gene Cards and TTD databases.Intersection targets were acquired after drug and disease target mapping.Then the protein-protein interaction network was constructed by String database to analyze the interactions and screened the core genes by topology.Finally,the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the core genes were carried out through Database for Annotation,Visualization,and Integrated Discovery.The visual network of“active ingredients-targets-signaling pathways”was constructed by Cytoscape3.6.0 software.Results A total of 47 ingredients and 34 core genes were obtained.GO enrichment analysis obtained 357 items(P<0.05),including 299 Biological Processes,21 Cellular Components and 37 Molecular Functions(P<0.05).And results of KEGG enrichment analysis showed 107 signaling pathways(P<0.05),including TNF signaling pathway,Toll-like receptor signaling pathway,and MAPK signaling pathway.Finally,the results suggested that the key active ingredients of CTWPGs included quercetin,luteolin,and triptolide.And core genes were PTGS2,JUN,AKT1,MAPK1,RELA,MAPK14,MAPK3 and TNF.The molecular mocking showed that luteolin and MAPK3,PTGS2,triptolide and MAPK3,TNF,kaempferol and MAPK14,GA30 and MAPK3,TNF,AKT1,PTGS2,baicalein and MAPK3 had good docking activity.Conclusion Network pharmacological studies showed that CTWPGs could play an intervention role in RA through multi-ingredients,multi-targets and multi-pathways,which had certain clinical application value.

关 键 词：复方雷公藤逐痛颗粒 类风湿关节炎 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]