基于网络药理学方法及分子对接技术探究清热祛湿汤治疗膝骨关节炎作用机制

Exploration of the Mechanism of Qingre Qushi Decoction in Treating Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking Technology

目的:采用网络药理学方法及分子对接技术研究清热祛湿汤治疗膝骨关节炎的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)数据库检索清热祛湿汤药物成分靶点;通过TTD、Genecards、OMIM数据库检索膝骨关节炎靶点;制作韦恩图获取药物-疾病交集靶点;通过Cytoscape3.9.0软件绘制药物有效成分-疾病-共同靶点网络图;利用String数据库构建蛋白相互作用(PPI)网络;使用R语言软件对交集靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析;使用AutoDockTools1.5.6等软件对药物主要有效成分与疾病核心靶蛋白进行分子对接验证。结果:清热祛湿汤的有效成分为槲皮素、木犀草素等;PPI网络构建获得的核心靶蛋白是蛋白激酶B抗体(AKT1)、纤溶酶原激活物抑制物1(SERPINE1)等;GO富集分析获得1902条GO条目;KEGG富集分析获得105条信号通路;将5种药物有效成分与5种核心靶蛋白进行分子对接,均具有较好的结合活性。结论:清热祛湿汤治疗膝骨关节炎具有多成分、多靶点、多途径的特点,具体通过发挥调控炎症反应、软骨基质降解、软骨细胞的凋亡和增殖等作用,延缓膝骨关节炎的进展。

Objective:To study the mechanism of Qingre Qushi Decoction in the treatment of knee osteoarthritis by network pharmacology and molecular docking technology.Methods:The drug component targets of Qingre Qushi Decoction were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database.TTD,Genecards and OMIM databases were used to search the targets of knee osteoarthritis.Making Venn diagram to obtain the intersection targets of drugsdiseases;Cytoscape3.9.0 software was used to map the effective ingredients of drugs-diseases-common targets network.The protein-protein interaction(PPI)network was constructed with String database.The intersection targets were enrichment analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)using R language software.Software such as AutoDockTools1.5.6 was used to verify the molecular docking between the main components of drugs and the core target proteins of diseases.Results:The key components of Qingre Qushi Decoction were quercetin,luteolin,etc..PPI network was constructed to obtain the core targets AKT serine/threonine kinase 1(AKT1),SERPIN family E member 1(SERPINE1),etc..A total of 1902 GO items were obtained by GO enrichment analysis,and 105 signaling pathways were obtained by KEGG enrichment analysis.Five main effective ingredients were used for docking with five core target proteins,and all of them had good binding activity.Conclusion:The treatment of knee osteoarthritis with Qingre Qushi Decoctionmay has the characteristics of multiple components,targets and pathways,through the regulation of inflammatory response,cartilage matrix degradation,chondrocyte apoptosis and proliferation,and so on,to delay the progression of knee osteoarthritis.