基于网络药理学研究人参治疗心肌纤维化的相关机制

Based on network pharmacology to study the related mechanism of ginseng in the treatment of myocardial fibrosis

目的运用网络药理学的方法探讨人参相关活性成分治疗心肌纤维化(myocardial fibrosis,MF)的分子作用机制。方法通过TCMSP数据库和文献挖掘获取人参的主要活性成分,利用人类基因数据库GeneCards预测和筛选人参活性成分的作用靶点。采用String数据库和Cytoscape 3.8.2软件绘制蛋白相互作用网络(PPI),借助DAVID 6.8数据库进行潜在基因的基因本体(GO)分析和基因组百科全书(KEGG)通路富集分析。结果筛选得到人参与MF相关的17个活性成分,涉及38个作用靶点。GO分析结果显示,人参治疗MF潜在基因的生物功能主要涉及影响核受体的活动,配体激活的转录因子活性,半胱氨酸型内肽酶活性参与凋亡信号通路,半胱氨酸型内肽酶活性参与凋亡过程,转录辅激活结合,G蛋白偶联的神经递质受体活性,类固醇结合,神经递质受体的活动,转录辅因子结合,G蛋白偶联胺受体活性等方面;KEGG通路富集分析结果显示,人参治疗MF在基因的通路主要涉及肿瘤坏死因子信号通路,弓形体病通路,流体剪切应力与动脉粥样硬化通路,前列腺癌通路,糖尿病并发症的AGE-RAGE信号通路,乙型肝炎通路,甲型流感通路,细胞凋亡通路,麻疹通路,军团病通路等。结论人参治疗MF是多成分、多靶点、多通路的复杂过程,主要通过参与抑制心肌炎症反应、NF-κB结合、多种受体的结合及磷酸化等发挥治疗MF的作用。

Objective:To explore the molecular mechanism of ginseng-related active ingredients in the treatment of myocardial fibrosis(MF) by means of network pharmacology.Methods:The main active ingredients of ginseng were obtained through the TCMSP database and literature mining,and the human gene database GeneCards was used to predict and screen the targets of the active ingredients of ginseng.Use String database and Cytoscape 3.8.2 software to draw protein interaction network(PPI),and use DAVID6.8 database for gene ontology(GO) analysis of potential genes and genome encyclopedia(KEGG)pathway enrichment analysis.Results:17 active ingredients related to human involvement in MF were screened,involving 38 targets.The results of GO analysis showed that the biological functions of ginseng in the treatment of MF potential genes mainly involve influencing nuclear receptor activity,ligandactivated transcription factor activity,cysteine-type endopeptidase activity involved in apoptosis signaling pathway,cysteine-type Endopeptidase activity is involved in the process of apoptosis,transcription co-activation binding,G protein-coupled neurotransmitter receptor activity,steroid binding,neurotransmitter receptor activity,transcription cofactor binding,G protein-coupled amine receptor activity and so on;KEGG pathway enrichment analysis results show that the gene pathways of ginseng treatment of MF mainly involve tumor necrosis factor signaling pathway,toxoplasmosis pathway,fluid shear stress and atherosclerosis pathway,prostate cancer pathway,and diabetes complications.AGE-RAGE signaling pathway,hepatitis B pathway,influenza A pathway,apoptosis pathway,measles pathway,legionnaires disease pathway,etc.Conclusion:The treatment of MF with ginseng is a complex process with multiple components,multiple targets and multiple pathways.It mainly participates in inhibiting myocardial inflammation,binding of NF-κB,binding of multiple receptors and phosphorylation to play a role in the treatment of MF.