基于网络药理学探讨新伤丸治疗膝骨性关节炎的分子作用机制  

A study on the molecular mechanism of Xinshang Wan on knee osteoarthritis based on the network pharmacology

作　　者：廖国平 胡军平 杨峰 欧礼 尹书东 胡建华 尹新生 LIAO Guoping

机构地区：[1]湖南省常宁市中医医院,湖南常宁421500

出　　处：《中医临床研究》2022年第1期28-32,共5页Clinical Journal Of Chinese Medicine

基　　金：湖南省中医药科研计划项目一般课题(D2022115);湖南省中医药科研计划项目一般课题(2017154);中国特色示范骨伤科建设项目;湖南省中医药重点研究室(詹氏正骨重点研究室);湖南省“十三五”省级中医重点专科建设项目(中药学)。

摘　　要：目的:基于网络药理学方法探讨新伤丸治疗膝骨性关节炎(Knee Osteoarthritis,KOA)的潜在分子作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)数据库检索新伤丸中16个药味中含有的活性成分,筛选有效活性成分及其潜在作用靶点;运用Gene Cards数据库获取与KOA相关的靶标基因,采用Cytoscape 3.6.3软件构建"药物-活性成分-靶点基因"网络;基于网络中的靶标基因,使用String在线平台进行蛋白质-蛋白质相互作用网络分析,采用Metascape数据库进行基因本体论(GO)富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。结果:通过筛选共得到159个有效活性成分,123个药物靶点,61个KOA相关且药物作用的靶标基因,60个蛋白质-蛋白质相互作用网络蛋白,15个网络核心蛋白,关键蛋白涉及白细胞介素(Interleukin,IL)-6、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、半胱氨酸蛋白酶3(Caspase 3,CASP3)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)8、表皮生长因子(Epidermal Growth Factor,EGF)、RELA癌基因(RELA Proto-Oncogene, NF-KB Subunit,RELA)和erb-b2受体酪氨酸激酶2(Erb-B2 Receptor Tyrosine Kinase 2,ERBB2)等;获得253条GO生物学过程(BP)和72条相关信号通路,涉及破骨细胞分化、MAPK信号通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、IL-17信号通路、Fox O信号通路、趋化因子信号通路、Ras信号通路、细胞凋亡和细胞衰老等。结论:新伤丸可能通过调控细胞增殖与凋亡、炎症反应等治疗KOA。Objective:To explore the potential molecular action mechanism of Xinshang Wan(新伤丸)on KOA.Methods:Through TCMSP database,the active compounds in 16 TCM medicines of Xinshang Wan were searched,and their effectively active components and potential action targets were screened.The targets genes related to KOA was obtained from GeneCards database,and the“medicineactive compound-target gene”network was constructed by Cytoscape 3.6.1 software.PPI network was analyzed on line by String database.The GO enrichment analysis and KEGG pathway enrichment analysis was conducted by Metascape database.Results:After screening,159 effectively active components and 123 medicine targets were obtained.A total of 61 targets genes were related to KOA,and 60 PPI network proteins were obtained.15 proteins were defined as the PPI network core nodes,involving in key proteins such as IL-6,VEGFA,CASP3,MAPK8,EGF,RELA,ERBB2 A,etc.253 GO biological processes and 72 KEGG signal pathways were obtained,including osteoclast differentiation,MAPK signal pathway,PI3 K-Akt signal pathway,TNF signal pathway,IL-17 signaling pathway,FoxO signaling pathway,chemokine signaling pathway,Ras signaling pathway,apoptosis,cellular senescence,etc..Conclusion:Xinshang Wan may regulate cell proliferation,cell apoptosis and inflammatory response to treat KOA.

关 键 词：新伤丸 网络药理学 膝骨性关节炎 信号通路 

分 类 号：R274.9[医药卫生—中西医结合]