基于网络药理学研究人参治疗糖尿病视网膜病变的作用机制

A study on the action mechanism of Renshen on diabetic retinopathy based on network pharmacology

目的:运用网络药理学探讨人参治疗糖尿病视网膜病变的作用靶点及信号通路。方法:通过中药系统药理学数据库与分析平台(TCMSP)、GeneCards、OMIM和TTD数据库,搜索获得人参活性成分、靶点,以及糖尿病视网膜病变的靶点。用R语言得到共有靶点后,运用Cytoscape 3.7.0软件建立“人参-活性成分-靶点-糖尿病视网膜病变”网络图。通过String数据库筛选关键靶点并获取蛋白质-蛋白质相互作用网络图。使用基因本体论(GO)、京都基因与基因组百科全书(KEGG)通路富集分析,得出人参治疗糖尿病视网膜病变的生物功能、相关通路。结果:得到人参治疗糖尿病视网膜病变的活性成分22个,与糖尿病视网膜病变的共同靶点42个。发现人参作用于糖尿病视网膜病变的关键节点半胱氨酸蛋白酶3(Caspase 3,CASP3)、转录因子p65(Transcription factor p65,RELA)、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)8等,并因此影响人体的核受体活性、类固醇激素受体活性等生物功能,以及EB病毒感染、肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、流体剪应力与动脉粥样硬化等信号通路,达到治疗糖尿病视网膜病变的效果。结论:初步探索人参治疗糖尿病视网膜病变的机制后发现,人参可能通过多途径抑制炎症反应、血管内皮增生和血栓形成从而治疗糖尿病视网膜病变,为后续临床试验提供了较为可靠的理论依据。

Objective:To explore the action targets and signaling pathways of Renshen(Ginseng)in the treatment of diabetic retinopathy by network pharmacology.Methods:The active ingredients and the targets of Renshen as well as the targets of diabetic retinopathy were searched and obtained by TCMSP,GeneCards,OMIM and TTD databases.After obtaining the common targets by R language,the network diagram of“Renshen-active ingredient-target-diabetic retinopathy”was established by Cytoscape 3.7.0 software.In String database,the key targets were screened and a PPI network diagram was obtained.The biological functions and related signaling pathways of Renshen in the treatment of diabetic retinopathy were obtained by the GO enrichment analysis and KEGG pathway enrichment analysis.Results:A total of 22 active ingredients of Renshen for the treatment of diabetic retinopathy were obtained,with 42 common targets of Renshen and diabetic retinopathy.It was found that the key nodes that Renshen effects on diabetic retinopathy were CASP3,RELA,MAPK8 and so on.It affects the biological functions of human body such as nuclear receptor activity,steroid hormone receptor activity,as well as the signaling pathways such as epstein-bar virus infection,TNF signaling pathway,fluid shear stress and atherosclerosis,so as to treat diabetic retinopathy.Conclusion:After initially exploring the mechanism of Renshen on diabetic retinopathy,it is found that Renshen may inhibit inflammatory response,vascular endothelial hyperplasia and thrombosis through multiple ways,so as to treat diabetic retinopathy,which provides a relatively reliable theoretical basis for subsequent clinical trials.