摘要
目的利用网络药理学和分子模拟对接的方法探究灵宝护心丹治疗急性心肌梗死(AMI)的分子机制。方法通过中药系统药理学数据库(TCMSP)、中医综合数据库(TCMID)获得灵宝护心丹所含9味中药相关活性化合物和作用靶点;通过人类基因数据库Gene Cards获得AMI相关基因,利用String 11.0数据库获得目标基因;利用Cytoscape 3.7.2软件构建化合物-靶标网络,根据拓扑学参数筛选灵宝护心丹治疗AMI的核心靶点;利用Cytoscape 3.7.2插件ClueGO+Cluepedia对疾病和药物交集靶点进行基因本体(GO)生物学过程富集分析和京都基因与基因组百科全书(KEGG)通路注释分析。结果灵宝护心丹化合物-AMI靶点网络包含57个疾病靶点和104个活性化合物,核心靶点包括叉头转录因子(FoxO1)、沉默信息调节因子1(Sirt1)、CASP3、白介素-6(IL-6)、AKT1、SOD2、Bcl2等。GO功能富集得到73个条目;KEGG富集到111个通路,并且被分类为16个具有统计学意义的亚组,主要涉及FoxO信号通路、HIF-1信号通路、凋亡信号通路、NF-κB信号通路等。使用GeneMANIA数据库构建核心靶标蛋白质-蛋白质相互作用(PPI)网络,并对其进行生物学功能分析。利用分子对接模拟软件Autodock Vina 1.1.2,对关键药效分子与核心靶标进行配体-受体对接模拟计算。结论基于网络药理学预测灵宝护心丹治疗AMI的潜在分子机制,为进一步研究其药效和作用机制奠定了基础。
Objective To explore the mechanism of Lingbao Huxin pills in the treatment of acute myocardial infarction(AMI)based on network pharmacology and molecular docking.Methods Nine active compounds and action targets of Lingbao Huxin pills were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and Traditional Chinese Medicines Integrated Database(TCMID).AMI-related genes were obtained from the human gene database Genecards,and target genes were obtained from the String 11.0 database.The compound-target network was constructed by Cytoscape 3.7.2 software,and the core targets of Lingbao Huxin pills in the treatment of AMI were screened according to the topological parameters.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway annotation analysis were performed on the intersection of disease and drug targets using Cytoscape 3.7.2 plugin ClueGo+Cluepedia.Results Fifty-seven protein targets and 104 active components of Lingbao Huxin pills were identified,and the core targets included FoxO1,Sirt1,CASP3,IL-6,AKT1,SOD2,Bcl2.Seventy-three items were obtained from GO functional enrichment.KEGG was enriched into 111 pathways,which were classified into 16 statistically significant subgroups,mainly involving FoxO signaling pathway,HIF-1 signaling pathway,apoptosis signaling pathway,NF-κB signaling pathway.The core target PPI network was constructed using Genemania database,and its biological function was analyzed.The molecular docking simulation software Autodock Vina 1.1.2 was used to simulate the ligand-receptor docking between key drug molecules and core targets.Conclusion This study predicted the potential molecular mechanism of Lingbao Huxin pills in the treatment of AMI and provide a foundation for further study of its efficacy and mechanism of action.
作者
谭宇
史大卓
柴华
马晓娟
TAN Yu;SHI Dazhuo;CHAI Hua;MA Xiaojuan(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)
出处
《中西医结合心脑血管病杂志》
2021年第7期1057-1069,共13页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金面上项目(No.81774141)。
关键词
急性心肌梗死
灵宝护心丹
网络药理学
作用机制
acute myocardial infarction
Lingbao Huxin pills
network pharmacology
mechanism
