基于网络药理学探讨杜仲治疗类风湿关节炎的作用机制

Discussion on mechanism of Duzhong in treating rheumatoid arthritis based on network pharmacology

目的:基于网络药理学探讨杜仲治疗类风湿关节炎(Rheumatoid Arthritis,RA)的作用机制。方法:通过中药系统药理学数据库和分析平台(TCMSP)筛选杜仲的活性成分及其作用靶点;利用GeneCards及OMIM数据库检索RA相关靶点基因,并借助String数据库、Cytoscape 3.7.1软件构建蛋白质-蛋白质相互作用网络、活性成分-靶点网络;通过David数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果:筛选后得到杜仲活性成分28个、作用靶点181个、RA相关靶点4822个、杜仲治疗RA的潜在作用靶点135个。包括丝氨酸/苏氨酸蛋白激酶1(Akt serine/Threonine kinase1,AKT1)、白细胞介素(Interleukin,IL)-6、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、IL-1β等。GO富集分析获得生物过程561条,细胞组分60条和分子功能117条。KEGG富集分析得到156条通路,涉及糖尿病并发症中的晚期糖基化终末产物(Advanced Glycation End Products,AGEs)-晚期糖基化终末产物受体(Receptor of AGEs,RAGE)信号通路、脂质和动脉粥样硬化、肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、IL-17信号通路、缺氧诱导因子-1(Hypoxia Inducible Factor-1,HIF-1)信号通路等。结论:杜仲通过多成分、多靶点、多通路发挥治疗作用,为临床应用提供理论依据。

Objective:To investigate the mechanism of Duzhong(Cortex Eucommlae)in treating RA through the network pharmacology.Methods:The active components and their targets of Duzhong were screened by TCMSP database.Gene Gards and OMIM databases were used to collect RA-related disease targets.String database and Cytoscape 3.7.1 software were used constructing protein-protein interaction network and active components-targets network.David database was used for GO and KEGG enrichment analysis.Results:After screening,28 active components of Duzhong were obtained,with 181 targets.There were 4822 RA targets,and 135 potential action targets of Duzhong in the treatment of RA,including AKT1,IL-6,VEGF,IL-1β,etc..GO analysis showed 561 biological process,60 cell components and 117 molecular functions.KEGG pathway enrichment analysis screened 156 pathways,involving AGES-RAGE signaling pathway in diabetic complications,Lipid and atherosclerosis,TNF signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway,etc..Conclusion:Duzhong plays a therapeutic role through multi-component,multi-target and multipathway,which provides theoretical basis for clinical application.