基于网络药理学的人参治疗非酒精性脂肪肝病靶点研究

Explain therapeutic target of Panax ginseng for nonalcoholic fatty liver disease through network pharmacology system

目的基于网络药理学研究人参对非酒精性脂肪肝病(NAFLD)的治疗靶点。方法利用网络药理学分析平台BATMAN-TCM获取人参活性成分及其对应靶点,使用Cytoscape软件对功能组-靶点基因-人参药物成分网络进行构建。对靶基因通过STRING平台构建出靶点群蛋白互作网络(protein protein interaction network,PPI),通过在线工具metascape对靶基因进行通路富集分析。从高通量基因表达数据库(Gene Expression Omnibus,GEO)下载人NAFLD转录组表达数据GSE89632,表达量进行标准化处理,使用双侧非配对t检验来检测表达差异的显著性。结果人参药物成分对脂肪代谢有显著影响,特别是脂肪酸降解。通过蛋白相互作用分析和通路富集分析,发现了31个人参药物成分的关键靶基因(ACADM、SCD、 ACACA、 ACSL1、 NR1H3、 LEP、 PPARA、 ADIPOQ、 NR1H4、 CEBPA、 HMGCR、 SREBF1、 TNF、 SREBF2、ESR1、 ABCA1、 INS、 AKT1、 AVP、 RXRA、 HSD17B6、 SRD5A2、 UGT1A1、 CYP19A1、 PTGS2、 CYP2E1、 HTR2A、HSD17B1、EDN1、CCL5、AGTR1)和NAFLD发病过程紧密相关。其中胰岛素(insulin,INS)的节点数量远高于其他靶基因,INS的mRNA表达量在NAFLD组织中显著上调(P<0.000 1)。结论 INS可能是人参治疗NAFLD的关键核心靶点之一。

Objective To study the drug-target-pathway and its mechanism of Panax ginseng active ingredients in the treatment of nonalcoholic fatty liver disease(NAFLD) based on network pharmacology.Methods BATMAN-TCM, a network pharmacological analysis platform, was used to obtain Panax ginseng active ingredients and their corresponding targets.Cytoscape software was used to construct a functional group-target gene-ginseng drug component network.Target group protein interaction network(PPI) was constructed by STRING platform for target genes.Metascape was an online tool for channel enrichment analysis of target genes.Human NAFLD transcriptome expression data GSE89632 was downloaded from the Gene Expression Omnibus(GEO) database.The expression level was standardized and the significance of expression difference was detected by bilateral unpaired t test.Results The components of Panax ginseng had significant effects on lipid metabolism, especially on fatty acid degradation.Through protein interaction analysis and pathway enrichment analysis, 31 key target genes(ACADM, SCD, ACACA, ACSL1, NR1 H3, LEP,PPARA, ADIPOQ, NR1 H4, CEBPA, HMGCR, SREBF1, TNF, SREBF2, ESR1, ABCA1, INS, AKT1, AVP, RXRA, HSD17 B6,SRD5 A2, UGT1 A1, CYP19 A1, PTGS2, CYP2 E1, HTR2 A, HSD17 B1, EDN1, CCL5, AGTR1) of Panax ginseng drug components were found to be involved in NAFLD pathway, which were closely related to the pathogenesis of NAFLD.The number of INS nodes was much higher than other target genes.The expression of INS was significantly up-regulated in NAFLD tissues(P < 0.000 1).Conclusion Ginseng has therapeutic effect on NAFLD, and INS may be the key target of ginseng in the treatment of NAFLD.