运用网络药理学和分子对接技术探究氧化苦参碱治疗骨关节炎的作用机制

Study on the Mechanism of Oxymatrine in the Treatment of Osteoarthritis by Using Network Pharmacology and Molecular Docking Technology

目的:运用网络药理学和分子对接探究氧化苦参碱(oxymatrine,OM)治疗骨关节炎(osteoarthritis,OA)的作用机制。方法:采用数据库平台Pharm Mapper和TCMSP预测OM的目标靶点,以“osteoarthritis”为关键词通过OMIM及Gene cards数据库平台检索OA相关基因,通过Venn图交集筛选出OM治疗OA的靶点;基于数据库平台STRING 10.0获取蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络并筛选核心靶点,利用David V 6.7在线网络平台进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,运用Cytoscape 3.7.1软件构建交集基因-GO-KEGG网络,最后借助Discovery Studio 2019将OM与核心靶点进行分子对接验证。结果:共得到OM治疗OA的交集靶点80个,筛选出5个核心靶点:AKT1、白细胞介素-6(interleukin-6,IL-6)、SRC、MYC和肿瘤坏死因子(tumor necrosis factor,TNF)。GO富集分析共得到119个条目,KEGG富集分析共得到129条通路,通过P值排序筛选出5条治疗OA的通路,分别是proteoglycans in cancer、PI3 K-Akt signaling pathway、Lipid and atherosclerosis、MAPK signaling pathway、Chemical carcinogenesis receptor activation、Prostate cancer,OM分别对接5个核心靶点的Libdockscore均高于92。结论:OM可稳定作用于多个靶点并激活多条通路干预OA。

Objective:To study the mechanism of oxymatrine(OM)in the treatment of osteoarthritis(OA)by using network phar-macology and molecular docking technology.Methods:The database platforms such as Pharm Mapper and TCMSP were used to predict the target targets of OM.With"osteoarthritis"as the keyword,OA related genes were retrieved through OMIM and Gene cards database platforms,and the targets of OM for the treatment of OA were screened through the intersection of Venn map.Based on the database platform of STRING 10.0,the protein-protein interaction(PPI)network was obtained and the core targets were screened.The GO and KEGG pathways enrichment analysis was conducted by using David V 6.7 online network platform.The in-tersection Gene-Go-KEGG network was constructed by using Cytoscape 3.7.1 software.Finally,OM was verified by molecular doc-king with the core targets with the help of Discovery Studio 2019.Results:A total of 80 intersection targets for OM treatment of OA were obtained,and five core targets were screened:AKT1,interleukin-6(IL-6),SRC,MYC and tumor necrosis factor(TNF)-α.A total of 119 entries were obtained from GO enrichment analysis,and 129 pathways were obtained from KEGG enrichment analy-sis.Five pathways for the treatment of OA were screened through P-value sequencing:proteoglycans in cancer,PI3K Akt signaling pathway,Lipid and atherosclerosis,MAPK signaling pathway,Chemical carcinogenesis receptor activation,Prostate cancer.Lib-dockscore of OM docking with five core targets were all higher than 92.Conclusion:OM can stably act on multiple targets and acti-vate multiple pathways to intervene in OA.