丹参-三七治疗膝骨关节炎的网络药理学机制研究

Study on Notwork PharmacologicalMechanismof Danshen and Sanqi in the Treatment of Knee Osteoarthritis

利用网络药理学和分子对接技术研究丹参-三七药对治疗膝骨关节炎(Knee osteoarthritis,KOA)的分子机制,为其临床应用提供理论支持。首先通过TCMSP数据库检索丹参-三七药对的主要活性成分和作用靶点;再利用GeneCards、OMIM和DisGeNET数据库检索KOA的相关靶点,使用维恩图得到丹参-三七药对和KOA的交集靶点;随后通过STRING数据库结合Cytoscape软件构建成分-靶点-疾病网络和PPI网络,筛选丹参-三七药对治疗KOA的核心成分和靶点;再通过DAVID数据库对交集靶点进行GO功能分析和KEGG通路富集分析,并使用AutoDock软件对核心成分和靶点进行分子对接。共筛选得到丹参、三七活性成分66个和相关靶点232个,药物和疾病交集靶点130个。槲皮素、木犀草素和丹参酮ⅡA为药物作用核心化合物,PTGS2、ADRB2和OPRM1为核心靶点。GO功能分析得到794个条目,KEGG分析得到相关通路141条。分子对接结果显示,丹参酮ⅡA与ADRB2有较好的亲和力。药对治疗KOA的机制主要涉及癌症途径、AGE-RAGE信号通路、脂质代谢和流体剪切力信号通路等,丹参酮IIA与ADRB2可能是关键作用成分和靶点。

To provide theoretical support for the clinical application of Danshen and Sanqi in the treatment of knee osteoarthritis(KOA),an exploration on the potential mechanism was performed using network pharmacology and molecular docking.TCMSP database was used to search the main compounds and related targets.GeneCards,OMIM,and DisGeNET databases were used to search the targets of KOA.The intersection targets of Danshen-Sanqi and KOA were obtained by Venn diagram.The composition-target-disease network and PPI network were constructed by using STRING database and Cytoscape software,and the core components and targets were screened.GO functional analysis and KEGG pathway enrichment analysis were performed through DAVID database.AutoDock software was used for molecular docking.A total of 66 active components and 232 related targets were obtained from Danshen-Sanqi.There were 130 intersection targets.Quercetin,luteolin,and tanshinone IIA were the core compounds,PTGS2,ADRB2 and OPRM1 were the core targets.GO functional analy-sis obtained 794 entries and KEGG analysis obtained 141 related pathways.Molecular docking results showed that tanshinone IIA had a good affinity with ADRB2.The mechanisms of Danshen-Sanqi treatment for KOA mainly involve cancer pathway,AGE-RAGE signaling pathway,lipid metabolism,fluid shear stress signaling pathways,etc.Tanshinone IIA and ADRB2 may be the key component and target.