摘要
目的:基于网络药理学探讨麻黄附子细辛汤治疗冠状动脉粥样硬化性心脏病(简称冠心病)的潜在作用机制。方法:应用中药系统药理学数据库及分析平台(TCMSP)、中药综合数据库(TCMID)获得麻黄附子细辛汤中药物主要成分,并通过TCMSP、Swiss Target Prediction数据库筛选相关作用靶点。利用OMIM、Gene Cards数据库筛选与冠心病相关靶点,通过Venny2.1工具获得两者交集。应用String平台构建靶点蛋白相互作用网络,通过Cytoscape3.7.2软件对药物、成分、靶点、疾病等数据构建相关网络并进行分析。利用DAVID6.8数据库对核心靶点进行基因本体(GO)富集分析及京都基因和基因组数据库(KEGG)通路分析。结果:筛选得到山奈酚、槲皮素、β-谷甾醇等35个化合物,242成分蛋白作用靶点;检索到载脂蛋白E、白细胞介素-6、血管紧张素转换酶等7 752个冠心病靶点;通过"药物-疾病"网络筛选到丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤抑制蛋白(Tumor Protein P53,TP53)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等193个作用靶点,这些靶点主要参与一氧化氮生物合成过程的正调控、对缺氧的反应、细胞凋亡过程的负调控等生物过程,对靶点进行富集发现药物通过调节HIF-1、Toll样受体、PI3k/Akt等信号通路发挥治疗冠心病的作用。结论:本研究揭示了麻黄附子细辛汤治疗冠心病通过多成分、多靶点、多途径的协同作用,为该复方在临床灵活应用提供一定的理论基础。
Objective:Explore the potential mechanism of the Mahuang Fuzi Xixin decoction(麻黄附子细辛汤) in treating coronary heart disease based on network pharmacology.Methods:The main components of the Mahuang Fuzi Xixin decoction were obtained by TCMSP and TCMID,and the related targets were screened by TCMSP and Swiss Target Prediction database.The targets related to coronary heart disease were screened by OMIM and Gene Cards database,and the intersection of them was obtained by Venny2.1 tool.The target protein interaction network was constructed by String platform,and the data of drugs,components,targets and diseases were constructed and analyzed by Cytoscape3.7.2 software.The GO enrichment analysis and KEGG pathway analysis of the core targets were carried out by using DAVID6.8 database.Results:35 compounds including kaempferol,quercetin and β-sitosterol were screened,and 7 752 targets for coronary heart disease such as apolipoprotein E,interleukin-6 and angiotensin converting enzyme were found.Through the “drug-disease” network,193 targets such as AKT1,TP53 and TNF were screened.These targets are mainly involved in the positive regulation of nitric oxide biosynthesis,the response to hypoxia,the negative regulation of apoptosis and other biological processes.By enriching the targets,it is found that drugs play a role in the treatment of coronary heart disease by regulating HIF-1,Toll-like receptors,PI3k/Akt and other signal pathways.Conclusion:This study reveals the synergistic effect of Mahuang Fuzi Xixin Decoction in the treatment of coronary heart disease through multi-components,multi-targets and multi-pathways,which provides a theoretical basis for the flexible clinical application of the compound.
出处
《中医临床研究》
2021年第23期5-9,共5页
Clinical Journal Of Chinese Medicine
基金
国家中医临床研究基地科研专项课题(2019JDZX003)。
