基于网络药理学探讨黄芪治疗病毒性心肌炎的作用机制
2021-02-18陈品良陈汉裕陈梓欣冼绍祥
陈品良 陈汉裕 陈梓欣 冼绍祥







摘要 目的:基于網络药理学对黄芪治疗病毒性心肌炎(VMC)的作用机制进行探讨。方法:在中药系统药理学数据库与分析平台(TCMSP)获取并筛选黄芪活性成分,获得对应的靶蛋白,并用Uniprot数据库将蛋白名称校正为基因符号,通过GeneCards、OMIM数据库筛选出VMC的相关基因,将黄芪的靶基因与VMC相关基因取交集获得黄芪治疗VMC的靶基因,使用Cytoscape 3.8.0构建“黄芪-活性成分-靶基因-VMC”网络,在STRING数据库下载PPI数据并利用R 4.0.0筛选出核心靶基因,利用R 4.0.0对黄芪治疗VMC的靶基因进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。结果:共获得黄芪活性成分20个,靶基因191个,VMC相关基因192个,取交集获得黄芪治疗VMC的靶基因34个,构建“黄芪-活性成分-靶基因-VMC”网络,VEGFA、AKT1、IL10、IL6、MMP9、TNF等可能是黄芪治疗VMC的核心靶基因。GO富集主要集中于细胞因子受体结合、细胞黏附的调节、对脂多糖的反应、对细菌来源分子的反应、细胞因子活性等方面。KEGG通路富集在AGE-RAGE信号通路(糖尿病并发症中)、IL17信号通路、乙型肝炎通路、甲型流感通路、查加斯病通路等。结论:本研究初步揭示了黄芪治疗VMC的核心靶基因和涉及的生物学过程及信号通路,为后续深入研究提供一定参考。
关键词 黄芪;病毒性心肌炎;靶基因;网络药理学;作用机制;活性成分;基因本体富集;京都基因和基因组百科全书通路富集
Investigation of Mechanisms of Radix Astragali seu Hedysari in the Treatment of Viral Myocarditis Based on a Network Pharmacology Approach
CHEN Pinliang1,CHEN Hanyu2,CHEN Zixin2,XIAN Shaoxiang2
(1 Guangzhou University of Chinese Medicine,Guangzhou 510405,China; 2 The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)
Abstract Objective:To investigate the mechanisms of Radix Astragali seu Hedysari in the treatment of viral myocarditis (VMC) based on a network pharmacology approach.Methods:Radix Astragali seu Hedysari′active ingredients were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP).The corresponding target proteins of active ingredients were obtained from TCMSP,and the protein names were corrected to gene symbols by using UniProt database.We obtained the related genes of VMC in GeneCards and OMIM database.The target genes of Radix Astragali seu Hedysari in the treatment of VMC were obtained by the intersection of the target genes of Radix Astragali seu Hedysari and the related genes of VMC.Using Cytoscape 3.8.0“Radix Astragali seu Hedysari-Active ingredient-Target gene-VMC” network was constructed.The PPI data were downloaded from STRING database and the core target genes were obtained through screening in R 4.0.0.R 4.0.0 was used to perform Go and KEGG pathway enrichment analysis on the target genes of Radix Astragali seu Hedysari in the treatment of VMC.Results:A total of 20 active ingredients and 191 target genes of Radix Astragali seu Hedysari were obtained while 192 related genes of VMC were obtained.A total of 34 target genes of Radix Astragali seu Hedysari in the treatment of VMC were obtained by intersection.The“Radix Astragali seu Hedysari-Active ingredient-Target gene-VMC” network was constructed.VEGFA,AKT1,IL10,IL6,MMP9,TNF,etc.may be the core target genes for Radix Astragali seu Hedysari in the treatment of VMC.The enrichment of GO is mainly concentrated in the cytokine receptor binding,regulation of cell-cell adhesion,response to lipopolysaccharide,response to molecule of bacterial origin,cytokine activity,etc..The enrichment of KEGG pathway was mainly concentrated in the AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,Hepatitis B,Influenza A,Chagas disease (American trypanosomiasis),etc.Conclusion:This study preliminarily reveals the core target genes,biological process and signal pathway of Radix Astragali seu Hedysari in the treatment of VMC,which provides reference for further research.
Keywords Radix Astragali seu Hedysari; Viral myocarditis; Target gene;Network pharmacology; Mechanism; Active ingredient; GO enrichment; KEGG pathway enrichment
中图分类号:R289.5;R735.7;R541文献标识码:Adoi:10.3969/j.issn.1673-7202.2021.23.015
病毒性心肌炎(Viral Myocarditis,VMC)是由病毒感染所致的弥漫性或局限性心肌炎症性疾病,以儿童和40岁以下的成年人居多,大多数患者可自愈,但其中一些可以迁延并发生各种心律失常,还有一些可以急性发作,导致心力衰竭,甚至猝死。……
