基于网络药理学和分子对接技术研究桂枝附子汤治疗类风湿关节炎的作用机制  

A study on the action mechanism of the Guizhi Fuzi decoction on rheumatoid arthritis based on network pharmacology and molecular docking technology

作　　者：韩磊[1] 郑福增[2] HAN Lei

机构地区：[1]河南中医药大学,河南郑州450000 [2]河南省中医院,河南郑州450000

出　　处：《中医临床研究》2022年第14期1-5,共5页Clinical Journal Of Chinese Medicine

基　　金：国家自然科学基金青年基金(81804050);2018年度河南省中医药科学研究重点课题(2018ZY1011)。

摘　　要：目的:基于网络药理学和分子对接技术探讨桂枝附子汤治疗类风湿关节炎的作用机制,为临床应用提供理论依据。方法:运用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索桂枝附子汤的活性成分和作用靶点,通过人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、药物基因组学知识库(PharmGkb)、药物和疾病数据库(DrugBank)、治疗目标数据库(DDT)收集疾病靶点。运用Cytoscape 3.6.1软件构建“活性成分-靶点”网络,借助STRING平台构建交集靶点的蛋白质-蛋白质相互作用网络,并使用Cytoscape对网络进行拓扑分析,获取核心基因,通过R语言进行进行基因本体论(GO)富集分析及京都基因和基因百科全书(KEGG)通路分析,最后将核心基因与主要活性成分进行分子对接验证。结果:经数据库预测得到桂枝附子汤治疗类风湿关节炎的有效成分154个,对应靶点138个;拓扑分析得到丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)1、丝裂原活化蛋白激酶3(MAPK3)、6号染色体的基因(Estrogen Receptor,ESR1)、信号转导和转录激活因子3(Signal Transducers and Activators of Transcription 3,STAT3)、肿瘤蛋白p53(Tumor Protein p53,TP53)、丝裂原活化蛋白激酶14(MAPK14)等14个核心基因;GO富集分析共涉及生物过程2315个,细胞组分74个,分子功能169个,KEGG通路富集分析筛选得到164条与类风湿关节炎相关通路,主要包括脂质和动脉粥样硬化信号通路、晚期糖基化终末产物-晚期糖基化终末产物受体(Advanced Glycation End Products-RAGE,AGEs-RAGE)信号通路、白细胞介素-17信号通路、肿瘤坏死因子信号通路等影响类风湿关节炎的发生。分子对接结果表明,主要活性化合物能够分别与核心靶点结合,并展现出较好的亲和力。结论:本研究对桂枝附子汤治疗类风湿关节炎的多成分、多�Objective:The action mechanism of the Guizhi Fuzi decoction(桂枝附子汤)on rheumatoid arthritis based on network pharmacology and molecular docking technology was explored to provide theoretical basis for its clinical application.Methods:The active ingredients and targets of the Guizhi Fuzi decoction were searched by TCMSP.The disease targets were collected in GeneCards,OMIM,PharmGkb,DrugBank and TTD databases.Cytoscape 3.6.1 software was used to construct the active component-target network,and STRING platform was used to build a protein-protein interaction network of intersection targets.Cytoscape software was used for a network topology analysis to obtain the core genes.The GO enrichment and KEGG pathway enrichment were analyzed by R language software,and finally the core genes were verified by molecular docking with the main active ingredients.Results:One hundred and fiftyfour active components and 138 corresponding targets of the Guizhi Fuzi decoction on rheumatoid arthritis were obtained by database prediction.The topological analysis revealed 14 core genes,including MAPK1,MAPK3,ESR1,STAT3,TP53,MAPK14 and so on.A total of 2315 biological processes,74 cell components and 169 molecular functions were involved in the GO enrichment analysis.164 pathways related to rheumatoid arthritis were screened by the KEGG pathway enrichment analysis.It mainly included lipid and atherosclerotic signaling pathways,AGEs-RAGE signaling pathways,Interleukin-17 signaling pathways,TNF signaling pathways and other pathways that affect the occurrence of rheumatoid arthritis.The molecular docking results showed that the main active compounds could bind to the core targets and showed good affinity.Conclusions:This study preliminarily explored the effects and action mechanisms of the Guizhi Fuzi decoction on rheumatoid arthritis by multiple components,multiple targets and multiple pathways,in order to provide more reference for following-up basic research and theoretical basis for its clinical application.

关 键 词：类风湿关节炎 桂枝附子汤 网络药理学 分子对接 

分 类 号：R593.22[医药卫生—内科学]