基于网络药理学和分子对接探讨补肾活血复方治疗心绞痛机制  

Exploration of the Mechanism of Bushenhuoxue Compound in the Treatment of Angina Pectoris Based on Network Pharmacology and Molecular Docking

作　　者：牛露霏 张艳[1] 王如意 NIU Lu-fei;ZHANG Yan;WANG Ru-yi(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《云南中医中药杂志》2023年第5期23-31,共9页Yunnan Journal of Traditional Chinese Medicine and Materia Medica

基　　金：国家自然科学基金项目(82174241);国家自然科学基金项目(81774157);国家重点研发计划中医药现代化研究(2019 YFC1708703);国家重点研发计划中医药现代化研究(2018YFC1707402);国家重点研发计划(2017YFC1700403)。

摘　　要：目的通过网络药理学方法和分子对接试验来探讨补肾活血复方治疗心绞痛的有效成分、作用靶点及作用通路。方法首先利用中药系统药理学数据库与分析平台(TCMSP)查找补肾活血复方的药物成分和药物靶点,并使用UniProt数据库对检索的药物靶点进行过滤筛选。然后通过GeneCards数据库、pharmGKB数据库、TTD数据库、Drugbank数据库检索来得到心绞痛的疾病靶点。最后将补肾活血复方的药物靶点与心绞痛的疾病靶点取交集,从而得到补肾活血复方治疗冠心病的作用靶点。利用Cytoscape3.9.0软件,构建“药物成分—作用靶点”网络关系图。在String网站绘制蛋白互作网络(PPI)并利用Cytoscape3.9.0软件联合R软件筛选PPI网络核心。对作用靶点进行GO富集分析和KEGG富集分析。之后通过AutoDock软件完成分子对接验证,在Pymol软件中绘制可视化分子对接图。结果得到补肾活血复方治疗心绞痛的入血成分109个,其中槲皮素、木犀草素、山奈酚、汉黄芩素为关键成分。药物—疾病交集靶点149个。对交集靶点GO富集结果显示,生物过程(BP)主要涉及到主要条目包括对氧气水平的反应、脂多糖的反应、对营养水平的反应、对氧化应激的反应、对细菌来源分子的反应等。得到细胞组分(CC)99条,主要条目包括薄膜阀、膜微区、水泡腔、质膜外侧、分泌颗粒管腔等。得到分子功能(MF)195条,主要条目包括DNA转录结合因子结合、RNA聚合酶II特异性DNA结合转录因子结合、核受体活性、配体激活的转录因子活、儿茶酚胺结合性等方面。KEGG分析主要富集在脂质与动脉粥样硬化通路。分子对接试验显示,关键活性成分与核心靶点通过氢键相链接,能够形成稳定的空间结构。结论网络药理学和分子对接结果表明补肾活血复方治疗心绞痛的机制在于应用槲皮素、木犀草素、山奈酚、黄芩素等活性成分,以AKT1�Objective:To study the effective components,targets and pathways of Bushenhuoxue Compound in the treatment of angina pectoris by means of network pharmacology and molecular docking test.Methods:Firstly,the pharmaceutical components and targets of Bushenhuoxui Compound were searched by using TCM system of Pharmacology Database and Analysis Platform(TCMSP),and the drug targets were filtered and screened by using UniProt database.Secondly,the disease targets of angina pectoris were obtained through GeneCards database,pharmGKB database,TTD database and Drugbank database.Finally,the drug target of Bushenhuoxue Compound was intersected with the disease target of angina pectoris,so as to obtain the effect targets of Bushenhuoxue Compound in treating coronary heart disease.Cytoscape3.9.0 software was used to construct the network diagram of drug components and target.The protein interaction network(PPI)was drawn on the String website and the PPI network core was screened by using Cytoscape3.9.0 software and R software.The effect targets were performed by GO enrichment analysis and KEGG enrichment analysis.After that,the molecular docking verification was completed by AutoDock software,and the visual molecular docking diagram was drawn in Pymol software.Results:109 blood components of Bushenhuoxuei Compound for the treatment of angina pectoris were obtained,among which quercetin,luteolin,kaempferol and baicalin were the key components.There were 149 drug-disease intersection targets.The GO enrichment results of intersection targets showed that biological processes(BP)mainly involved the main items including the response to oxygen level,lipopolysaccharide response,response to nutrient level,response to oxidative stress,response to bacterial-derived molecules,etc.99 cell components(CC)were obtained,and the main items included membrane valve,membrane microregion,vesicular cavity,plasma membrane lateral,secretion granule lumen,etc.195 items of molecular function(MF)were obtained,including the combination of DNA transcription

关 键 词：补肾活血复方 心绞痛 网络药理学 分子对接 

分 类 号：R541.1[医药卫生—心血管疾病]