基于网络药理学研究温胆汤治疗冠心病的作用机制

Study on the Mechanism of Wendan Decoction in the Treatment of Coronary Heart Disease Based on Network Pharmacology

目的:基于网络药理学研究温胆汤治疗冠心病的作用机制。方法:以化合物的口服药物生物利用度(OB)和类药性(DL)为标准,借助中药系统药理学分析平台(TCMSP)、OMIM和Genecards数据库、反向分子对接服务器(DRAR-CPI)筛选并预测温胆汤的活性成分及治疗冠心病的作用靶标。借助Cytoscape 3.6.0软件构建温胆汤活性成分-冠心病作用靶标网络;借助STRING数据库构建靶蛋白相互作用(PPI)网络,筛选连接度(PPI网络中节点通过边的个数)排名前5的靶蛋白,并利用分子对接服务器预测其与活性成分的结合活性。通过生物学信息注释数据库(DAVID)对靶点基因本体(GO)生物过程和京都基因与基因组百科全书(KEGG)中代谢通路进行分析。结果:从温胆汤中共筛选出147个活性成分,143个与冠心病相关的作用靶点,包括白蛋白、载脂蛋白E、白细胞介素6、肿瘤坏死因子、C反应蛋白等。经分子对接分析,温胆汤活性成分与靶蛋白结合能力较强。经GO和KEGG通路富集分析,参与RNA聚合酶Ⅱ启动子转录调控、胆固醇代谢、低氧反应、药物反应、炎症反应等多种生物过程,调节包括脂肪细胞脂解作用通路、细胞因子-细胞因子受体相互作用通路、脂肪消化与吸收通路、过氧化物酶体增殖物激活受体信号通路、肾素-血管紧张素等通路。结论:温胆汤的活性成分能通过多个靶点、多条通路发挥治疗冠心病的作用,本研究结果为进一步研究温胆汤的药理作用提供了参考依据。

OBJECTIVE：To study the mechanism of Wendan decoction in the treatment of coronary heart disease based on network pharmacology. METHODS：Using oral bioavailability（OB）and drug like（DL）as reference,the active components of Wendan decoction,targets for treatment of coronary heart disease were screened and predicted by utilizing TCMSP,OMIM and Genecards database,DRAR-CPI. Cytoscape 3.6.0 software was adopted to construct an active component-coronary heart disease target network. The protein-protein interaction（PPI）network was established by using STRING database. Top 5 target proteins in the list of connectivity（the number of nodes passing through edges in PPI network）were screened. The activities of target protein with active components were predicted by molecular docking server. DAVID database was used to analyze metabolism pathway in target gene ontology （GO） biological process,Kyoto encyclopedia of genes and gnomes （KEGG）. RESULTS：A total of 147 active components and 143 targets related to coronary heart disease were screened,including albumin,apolipoprotein E,IL-6,TNF and C reactive protein,etc. After molecular docking analysis,the binding ability of active ingredients to target proteins was strong. Through GO and KEGG pathway enrichment analysis,active components participated in RNA polymerase Ⅱ promoter transcription regulation, cholesterol metabolism, hypoxia, drug reaction, inflammation and other biological processes, and regulated fat cell lipolysis pathway, cytokine-cytokine receptor interaction pathway, fat digestion and absorption pathway, peroxisome proliferator-activated receptor signaling pathway,renin-angiotensin pathway and so on. CONCLUSIONS：The active components of Wendan decoction play a role in the treatment of coronary heart disease through multiple targets and pathways. The results of this study provide a reference for further study of the pharmacological effect of Wendan decoction.