基于网络药理学的生脉饮(党参方)治疗动脉粥样硬化性心血管疾病的潜在分子机制

Mechanism of Shengmaiyin(Dangshen Prescription)in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology

目的:运用网络药理学方法,研究生脉饮(党参方)治疗动脉粥样硬化性心血管病(ASCVD)的活性成分、作用靶点和分子通路,揭示生脉饮(党参方)治疗ASCVD的分子机制,并为组方配伍的合理性阐释提供依据。方法:借助中西医结合数据库(SymMap),中药系统药理学技术平台(TCMSP)以及BATMAN-TCM平台获取生脉饮(党参方)主要化学成分,SymMap和中医药百科网站(ETCM)检索化合物靶点,借助疾病相关的基因与突变位点数据库(DisGeNET)和基因组注释(GeneCards)数据库检索疾病靶点;化合物靶点与疾病靶点作交集得到生脉饮(党参方)作用于ASCVD的预测靶点。利用蛋白质相互作用(STRING)数据库构建靶蛋白相互作用(PPI)网络图,借助Cytoscape软件获取生脉饮(党参方)作用于ASCVD的关键化合物和关键靶点,最后用The Database for Annotation,Visualization and Integrated Discovery(DAVID)网站将富集到的关键靶点进行基因本体(GO)生物学过程分析和京都基因与基因组百科全书(KEGG)通路分析。结果:生脉饮(党参方)作用于ASCVD的关键化合物有33个,关键靶点有25个。GO分析结果显示,生脉饮(党参方)治疗ASCVD关键靶点的生物功能主要涉及凋亡过程的调控、炎症反应、一氧化氮合成的调节、胰岛素分泌的调节等生物学过程;KEGG通路主要富集到磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)信号通路、凋亡信号通路、肿瘤坏死因子(TNF)信号通路、雌激素信号通路等20条信号通路。结论:本研究通过网络药理学从分子水平探讨生脉饮(党参方)治疗ASCVD的活性成分与潜在靶点,初步验证了生脉饮(党参方)的作用机制,并为进一步深入探究其作用机制奠定了理论基础。

Objective:By means of network pharmacology,the active ingredients,targets and molecular pathways of Shengmaiyin(Dangshen prescription)in the treatment of atherosclerotic cardiovascular disease(ASCVD)were studied,in order to reveal the molecular mechanism of Shengmaiyin(Dangshen prescription)in the treatment of ASCVD,and provide the rational explanation of the compatibility of the combination.Method:The main chemical components of Shengmaiyin(Dangshen prescription)were obtained by means of SymMap database,traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)platform and BATMAN-TCM platform.Compound targets were retrieved by SymMap and the Encyclopedia of Traditional Chinese Medicine(ETCM),and disease targets were retrieved by DisGeNET and GeneCards databases.The intersections of compound targets and disease targets were used to obtain the predicted targets of song-decoction on ASCVD.The Protein-Protein Interaction(PPI)network diagram was constructed through STRING database,and key compounds and targets of Shengmaiyin(Dangshen prescription)acting on ASCVD were obtained through Cytoscape.Finally,the enriched key targets were put for Gene Ontology(GO)biological process analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis through the Database for Annotation,Visualization and Integrated Discovery(DAVID).Result:There were 33 key compounds and 25 key targets of Shengmaiyin(Dangshen prescription)for ASCVD.The GO analysis showed that the biological functions of Shengmaiyin(Dangshen prescription)in the treatment of key ASCVD targets mainly involved biological processes,such as the regulation of apoptosis,inflammatory response,regulation of nitric oxide synthesis and regulation of insulin secretion.The KEGG pathway was mainly enriched in 20 signaling pathways,including tumor necrosis factor(TNF)signaling pathway,phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway,apoptosis signaling pathway and estrogen signaling pathway.Conclusion:Through network pharmacology,this study explored active ingredients and potential targets of Shengmaiyin(Dangshen prescription)in the treatment of ASCVD at the molecular level,preliminarily verified the mechanism of action of Shengmaiyin(Dangshen prescription),and laid a theoretical foundation for further study on the mechanism of action.