基于网络药理学和分子对接研究当归四逆汤治疗稳定型心绞痛的作用机制  

Study on Action Mechanism of Chinese Angelica Frigid Extremities Decoction in Treating Stable Angina Pectoris Based on Network Pharmacology and Molecular Docking

作　　者：王镕 况春燕[2] WANG Rong;KUANG Chunyan(Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou,China,550025;Guizhou Provincial People′s Hospital,Guiyang,Guizhou,China,550002)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州省人民医院,贵州贵阳550002

出　　处：《河南中医》2024年第12期1880-1887,共8页Henan Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81560056);贵州省第十二批优秀青年科技人才项目{黔科合平台人才[2019]5662};贵州省科技计划项目{黔科合基础[2018]1097};贵州省留学人员科技活动择优资助项目{黔人项目资助合同[2018]0003号};贵州省科技平台及人才团队计划项目(黔科合平台人才2017-5405)。

摘　　要：目的:基于网络药理学与分子对接研究当归四逆汤治疗稳定型心绞痛(stable angina pectoris,SAP)的作用机制。方法:使用SyMmap数据库和中药系统药理学数据库与分析平台检索当归四逆汤组方中药甘草、大枣、当归、桂枝、细辛、通草和白芍的化学成分及相关靶点;在GeneCards数据库获取SAP相关疾病靶点;取SAP疾病相关靶点和当归四逆汤组方中药活性成分相关靶点的交集,即为当归四逆汤治疗SAP的潜在靶点,并绘制韦恩图。利用STRING 11.5数据库对潜在靶点进行蛋白质相互作用(protein protein interaction,PPI)网络分析并筛选核心靶点。采用Cytoscape 3.10.1构建“中药-活性成分-潜在靶点”网络,并筛选关键成分。采用Matascape对潜在靶点进行基因本体(Gene Ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析。利用PyMOL4.6.0对关键靶点和成分进行分子对接。结果:从当归四逆汤组方中药共筛选得到155种化学成分及1728个相关靶点;在GeneCards数据库获得SAP相关靶点1089个;取交集得到当归四逆汤治疗SAP的潜在靶点121个。PPI网络分析发现信号传导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)、B细胞淋巴因子2(B cell lymphoma 2,BCL2)、蛋白激酶B1(protein kinase B1,PKB1,又称AKT1)等为核心靶点;“中药-活性成分-潜在靶点”网络分析筛选出槲皮素、山柰酚、β-谷甾醇等为关键成分。GO分析得到4688个生物过程,404个细胞组分和715个分子功能;KEGG分析得到磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)-AKT、缺氧诱导因子1(hypoxia-inducible factor 1,HIF1)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等200条信号通路。分子对接显示活性成分与靶点对接良好。结论:当归四逆汤中的多个化学成分通过调控多个相关靶点参与多条信号通路发挥治疗SAP的作Objective:To study on the action mechanism of Chinese Angelica Frigid Extremities Decoction in treating stable angina pectoris(SAP)based on network pharmacology and molecular docking.Methods:The chemical components of Chinese Angelica Frigid Extremities Decoction,composed of Gancao(Radix Glycyrrhizae),Dazao(Fructus Jujubae),Danggui(Radix Angelicae Sinensis),Guizhi(Ramulus Cinnamomi),Xixin(Radix et Rhizoma Asari),Tongcao(Medulla Tetrapanacis)and Baishao(Radix Paeoniae Alba)were retrieved from the SyMmap and TCMSP databases.Active ingredient-related targets were identified using the Metascape database.SAP-related disease targets were collected from the GeneCards database.The intersection of SAP-related and active ingredient-related targets was identified as potential therapeutic targets,and a Venn diagram was generated.Protein-protein interaction(PPI)network analysis of potential targets was performed using STRING 11.5,and core targets were identified.A"Chinese medicinal-active ingredient-potential target"network was constructed using Cytoscape 3.10.1 to screen key compounds.Gene Ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were conducted using Metascape.Molecular docking of key targets and ingredients was performed using PyMOL4.6.0.Results:A total of 155 chemical components and 1728 related targets were identified from Chinese Angelica Frigid Extremities Decoction.From the GeneCards database,1089 SAP-related targets were obtained.The intersection yielded 121 potential therapeutic targets for SAP.PPI network analysis revealed interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and IL-1β,etc.as core targets.The"Chinese medicinal-active ingredient-potential target"network identified quercetin,kaempferol,andβ-sitosterol,etc.as key components.GO analysis yielded 4688 biological processes,404 cellular components,and 715 molecular functions.KEGG analysis identified 200 signaling pathways,including phosphoinositide 3-kinase(PI3K-AKT),hypoxia-inducible fact

关 键 词：当归四逆汤 稳定型心绞痛 网络药理学 分子对接 张仲景 《伤寒论》 

分 类 号：R285[医药卫生—中药学]