基于网络药理学及分子对接探究脊蛇祛湿胶囊君药金毛狗脊与乌梢蛇治疗KOA的作用机制  

Action mechanism of Cibotium barometz and Zaocys dhumnades in the treatment of KOA based on network pharmacology and molecular docking

作　　者：张翠 喻杨 姚血明 黄聪 罗进芳 ZHANG Cui;YU Yang;YAO Xueming;HUANG Cong;LUO Jinfang(Guizhou University of Traditional Chinese Medicine,Guiyang 550002,China;Department of Rheumatism and Immunology,the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China;Guizhou Genuine Herbs Utility Consistency Research Center,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州中医药大学第二附属医院风湿免疫科,贵州贵阳550025 [3]贵州中医药大学贵州省道地药材性效用一致性研究中心,贵州贵阳550025

出　　处：《贵州科学》2025年第1期31-37,共7页Guizhou Science

基　　金：贵州省基础研究(自然科学)项目(项目编号:黔科合基础-ZK[2022]一般477);贵州中医药大学国家与省级科技创新人才团队培育项目(贵中医TD合字[2022]004号);贵州省科技计划项目(编号:黔科合基础-ZK[2021]一般537);贵州省普通高等学校特色重点实验室(编号:黔教合KY字[2017]006)。

摘　　要：目的:通过构建“药物-成分-疾病-靶点”的相互作用网络,探讨脊蛇祛湿胶囊中君药治疗膝骨关节炎(keen osteoarthritis,KOA)的作用机制。方法:通过Herb数据库及文献报道对金毛狗脊与乌梢蛇的化合物进行筛选,接着在PubChem数据库中下载化合物的分子结构式,把它们导入SwissTargetPrediction数据库得到化合物对应靶点,在GeneCards、OMIM数据库得到疾病有关靶点;应用在线作图软件Venny2.1.0得到药物与KOA的交集靶点;运用Cytoscape3.10.0软件建立“药物-成分-交集靶点”网络图;利用String平台和Cytoscape3.10.0软件作出蛋白与蛋白相互作用(protein-protein interaction,PPI)网络图;在DAVID数据库对交互靶点进行GO和KEGG富集分析;最后运用CB-DOCK2对主要成分和关键靶点进行分子对接。结果:共得到药物靶点562个,KOA靶点1244个,两个交互靶点126个;药物的主要成分是亚油酸、亚油酸甲酯、山柰酚、brachy stemidines A;关键靶点是IL-6、STAT3、CTNNB1、AKT1、MMP9;KEGG富集分析一共得到157条通路,与KOA有关的通路是脂质和动脉粥样硬化、AGE-RAGE信号通路、癌症通路。分子对接得出,主要成分皆能与关键靶点结合,且都有很好的结合能力。结论:本研究利用网络药理学方法揭示了金毛狗脊和乌梢蛇对KOA的多靶点、多通路治疗机制,为KOA临床治疗提供了理论基础。By constructing the drug-component-disease-target interaction network,the action mechanism of Cibotium barometz and Zaocys dhumnades in the treatment of knee osteoarthritis(KOA)was discussed.The compounds of Cibotium barometz and Zaocys dhumnades were screened out from Herb database and literature reports.The molecular structures of the compounds were downloaded from PubChem database,and were imported into SwissTargetPrediction database to obtain the corresponding targets of the compounds.The disease-related targets were obtained in GeneCards and OMIM databases.The intersection targets of drug and KOA were obtained by using software Venny2.1.0.Cytoscape3.10.0 software was used to establish the drug-component-intersection target network.String platform and Cytoscape 3.10.0 software were used to construct the protein-protein interaction(PPI)network.GO and KEGG enrichment analysis was performed on the interactive targets in DAVID database.Finally,CB-DOCK2 was used to perform molecular docking of the main components and key targets.A total of 562 drug targets,1244 KOA targets and 126 interactive targets were obtained.The main components of the drug were linoleic acid,linoleic acid methyl ester,kaempferol and brachy stemidines A.The key targets were IL-6,STAT3,CTNNB1,AKT1 and MMP9.A total of 157 pathways were obtained by KEGG enrichment analysis.The pathways related to KOA were lipid and atherosclerosis,AGE-RAGE signaling pathway,and cancer pathway.Molecular docking showed that the main components could bind to the key targets and had good binding ability.This study reveals the multi-target and multi-pathway treatment mechanism of Cibotium barometz and Zaocys dhumnades on KOA by using network pharmacology method,which provides a theoretical basis for the clinical treatment of KOA.

关 键 词：膝骨关节炎 金毛狗脊 乌梢蛇 脊蛇祛湿胶囊 分子对接 

分 类 号：R593[医药卫生—内科学]