膝痹通方治疗膝骨关节炎作用机制的网络药理学研究  

Network Pharmacological Study on Mechanism of Xibitong Decoction in Treatment of Knee Osteoarthritis

作　　者：李彦 王向红 何名江[1] 刘兴兴 赵传伟 郭宵飞 张洪美[1] LI Yan;WANG Xianghong;HE Mingjiang;LIU Xingxing;ZHAO Chuanwei;GUO Xiaofei;ZHANG Hongmei(Department One of Arthropathy,Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China;Department of Surgery,Yinchuan Hospital of Traditional Chinese Medicine,Yinchuan 750001,China)

机构地区：[1]中国中医科学院望京医院关节一科,北京100102 [2]银川市中医医院外科,银川750001

出　　处：《医学综述》2023年第4期802-810,共9页Medical Recapitulate

基　　金：首都卫生发展科研专项项目(首发2020-2-4161);中国中医科学院科技创新工程(CI2021A02005);北京市科技计划课题(Z201100005520058)。

摘　　要：目的探讨膝痹通方中“牛膝-独活-木瓜”治疗膝骨关节炎(KOA)的网络药理学作用机制。方法检索中药系统药理学数据库及分析平台中牛膝、独活、木瓜的主要化学成分,检索时限为2021年1月1日至3月26日。通过Gene Cards、TTD、DRUGBANK和OMIM数据库收集KOA疾病基因。然后将药物与疾病靶点进行映射,获得交集靶点即为“牛膝-独活-木瓜”作用于KOA的预测靶点。通过Cytoscape 3.6.0软件构建药物活性成分-靶点网络模型,选出关键有效成分。利用STRING数据库构建交集靶点蛋白质-蛋白质相互作用网络,选出关键蛋白。借助Web Gestalt、Metascape等在线工具对靶标基因进行基因本体和京都基因与基因组百科全书通路富集分析,筛选差异有统计学意义的通路。结果膝痹通方中“牛膝-独活-木瓜”治疗KOA的主要活性成分为檞皮素、汉黄芩素、表儿茶素、β-谷甾醇、山柰酚、二氢欧山芹醇醋酸酯、白桦脂酸等,核心靶点有JUN、肿瘤坏死因子、丝氨酸/苏氨酸蛋白激酶1、肿瘤蛋白p53、v-rel网状内皮细胞过多症病毒癌基因同源物A、重组人促分裂原活化的蛋白激酶(MAPK)1、白细胞介素-6、血管内皮生长因子A、Myc原癌基因蛋白、MAPK14等。膝痹通方治疗KOA的生物学通路主要与癌症、代谢、炎症、病毒等通路相关,其中最显著的是癌症信号通路。结论膝痹通方“牛膝-独活-木瓜”能通过多成分、多靶点、多通路起到治疗KOA的作用,为膝痹通方组方治疗KOA提供了有力的证据。Objective To investigate the network pharmacological mechanisms of"Achyranthes bidentata-Angelica pubescens-Fructus chaenomelis"in Xibitong decoction in the treatment of knee osteoarthritis(KOA).Methods The main chemical constituents of Achyranthes bidentata,Angelica pubescens and Fructus chaenomelis were searched in traditional Chinese medicine systems pharmacology database and analysis platform from Jan.1st to Mar.26th in 2021.KOA disease genes were collected through Gene Cards,TTD,DRUGBANK and OMIM databases.Then the drug and disease targets are mapped,and the intersection target is the prediction target of"Achyranthes bidentata-Angelica pubescens-Fructus chaenomelis"acting on KOA.Cytoscape 3.6.0 software was used to build the network model of"drug active ingredients-target",and the key active ingredients were selected.The intersection target protein-protein interaction network was constructed using the STRING database to select the key proteins.Online tools such as Web Gestalt and Metascape were used for Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analysis of target genes to screen the pathways with statistical differences(P<0.05).Results The main active ingredients of"Achyranthes bidentata-Angelica pubescens-Fructus chaenomelis"of Xibitong decoction in the treatment of KOA were quercetin,wogonin,epicatechin,β-sitosterol,kaempferol,O-acetylcolumbianetin,betulinic acid,etc.;the core targets were JUN,tumor necrosis factor,serine/threonine-protein kinase 1,tumor protein p53,v-Rel reticuloendotheliosis viral oncogene homolog A,mitogen-activated protein kinase(MAPK)1,interleukin-6,vascular endothelial growth factor A,Myc proto-oncogene protein,MAPK14,etc.The biological pathways of Xibitong decoction in the treatment of KOA were mainly related with cancer,metabolism,inflammation,and virus pathways,among which the most significant is the cancer signaling pathway.Conclusion Xibitong decoction"Achyranthes bidentata-Angelica pubescens-Fructus chaenomelis"can play a role in the treatment

关 键 词：膝骨关节炎 膝痹通方 牛膝 独活 木瓜 网络药理学 

分 类 号：R274[医药卫生—中医骨伤科学]