基于网络药理学方法对芪归八味汤治疗病毒性心肌炎作用机制的分析

Analysis of the mechanism of Qigui Bawei decoction in the treatment of viral myocarditis based on net⁃work pharmacology

目的基于网络药理学方法分析芪归八味汤治疗病毒性心肌炎(VMC)的作用机制。方法在中药系统药理学数据库与分析平台、中药分子机制的生物信息学分析工具数据库中收集芪归八味汤的化学成分和作用靶点,通过UniProt数据库对得到的靶点进行基因注释。在OMIM和GeneCards数据库中查找VMC的疾病靶点,与药物靶点进行韦恩分析,确定药物—疾病共同靶点。利用String平台对获得的相应靶点进行蛋白质相互作用(PPI)网络分析,筛选核心靶点,利用R软件对核心靶点进行基因本体(GO)功能和京都基因和基因组百科全书(KEGG)通路富集分析。结果筛选得到芪归八味汤中主要活性成分有78种,药物靶点479个,疾病靶点1 058个,药物—疾病共同靶点124个。PPI网络图包括124个节点、479条边,筛选出核心靶点19个。核心靶点的GO功能富集分析得到2 739个条目,在生物学过程中富集2 502条路径,主要参与对细菌来源分子的反应、对脂多糖的反应、对氧化应激的反应、外源性凋亡信号通路等过程;在细胞成分中富集92条路径,主要涉及薄膜筏、膜微域、膜区域等部位;在分子功能中富集145条路径,主要涉及受体配体活动、细胞因子受体结合等方面。KEGG通路富集分析结果显示,核心靶点涉及的通路主要有糖尿病并发症中的AGE/RAGE信号通路、MAPK信号通路、肿瘤坏死因子(TNF)信号通路、白细胞介素17(IL-17)信号通路等。结论芪归八味汤中的活性成分可通过调节AGE/RAGE、MAPK、TNF、IL-17信号通路等发挥治疗VMC的作用。

Objective To analyze the mechanism of Qigui Bawei decoction in the treatment of viral myocarditis(VMC)based on network pharmacology.Methods The chemical components and action targets of Qigui Bawei decoc⁃tion were collected from the pharmacology database and analysis platform of Chinese medicine system and the bioinformat⁃ics analysis tool database of Chinese medicine molecular mechanism,and gene annotation was performed on the obtained targets through Uniprot database.The disease targets of VMC were searched in OMIM and GeneCards databases,and Wayne analysis was conducted with drug targets to determine the drug-disease common targets.Protein-protein interaction(PPI)network was performed on the obtained corresponding targets using String platform,and core targets were screened out.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on core targets using R software.Results Seventy-eight kinds of main active ingredients,479 drug tar⁃gets,1058 disease targets and 124 drug-disease common targets in Qigui Bawei decoction were screened out.PPI network included 124 nodes,479 edges,and 19 core targets were screened out.The GO functional enrichment analysis of core tar⁃gets obtained 2739 items,and 2502 pathways were enriched in biological processes,which were mainly involved in the reaction to bacterial origin molecules,reaction to lipopolysaccharide,reaction to oxidative stress,exogenous apoptotic signaling pathways and other processes.Ninety-two pathways were enriched in cell components,mainly involving membrane rafts,membrane microdomains,membrane regions,etc.One hundred and forty-five pathways were enriched in molecular functions,mainly involving receptor ligand activity and cytokine receptor binding.KEGG pathway enrichment analysis showed that the core targets mainly involved the AGE/RAGE signaling pathway,MAPK signaling pathway,tumor necrosis factor(TNF)signaling pathway,interleukin 17(IL-17)signaling pathway and so on in diabetes complications.Conclu⁃sion The active ingredients in Qigui Bawai decoction can play a role in the treatment of VMC by regulating AGE/RAGE signaling pathway,MAPK signaling pathway,TNF signaling pathway and IL-17 signaling pathway.