基于网络药理学技术研究桃红四物汤延缓成纤维细胞生长的分子靶标  

Study on molecular target of Taohong Siwu Decoction in delaying growth of fibroblasts based on network pharmacology

作　　者：马进 李振万 罗月中[1] 江湧[1] 匡忠生[1] 谢宇晖[1] MA Jin;LI Zhen-wan;LUO Yue-zhong;JIANG Yong;KUANG Zhong-sheng;XIE Yu-hui(the First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州中医药大学第一临床医学院,广东广州510405

出　　处：《中国中药杂志》2020年第17期4120-4128,共9页China Journal of Chinese Materia Medica

基　　金：广东省自然科学基金项目(2015A030313349)。

摘　　要：桃红四物汤(Taohong Siwu Decoction,THSWD)作为活血化瘀方,对于延缓肾脏纤维化的进程有一定作用,但作为包含诸多单体成分的中药复方,应对复杂的病理过程,其研究方法的探讨和作用靶点的找寻一直是该方向的研究热点。活血化瘀法在阻滞IgA肾病(IgA nephropathy,IgAN)纤维化进程方面有一定的临床疗效,但作用机制尚不明确。该研究先借助网络药理学方法,研究THSWD干预IgAN纤维化进程的有效活性成分,作用靶点及分子作用机制,在此基础上,通过离体实验,验证THSWD作用于3T3细胞对ERK因子表达的影响。通过中药系统药理学技术平台收集THSWD中的活性成分及作用靶点,筛选得到木犀草素、槲皮素等61个有效活性成分及240个作用靶点,与CTD数据库查找的IgAN相关靶点相交得到185个靶点。利用Cytoscape软件与STRING数据库构建"桃红四物汤-活性成分-靶点"网络和蛋白互作网络,筛选69个核心靶点;通过DAVID对核心靶点的GO富集分析和KEGG通路分析及进行细胞实验,结果表明,ERK因子是THSWD干预IgAN重要的因子,THSWD可以显著降低细胞活性、ERK1/2 mRNA表达、p-ERK1/2蛋白表达。该研究提示,THSWD可能通过影响ERK因子及其磷酸化水平,来延缓成纤维细胞生长。As a prescription for promoting blood circulation and removing blood stasis,Taohong Siwu Decoction(THSWD)has certain effects in delaying the progression of renal fibrosis.However,as a traditional Chinese medicine compound containing many monomer components,it has been a research hotspot in the field of exploring the research methods and targets for the complex pathological process.The method of activating blood circulation and removing blood stasis has certain clinical effect in retarding the process of IgA nephropathy(IgAN)fibrosis,but the mechanism of action is still unclear.In this study,the network pharmacology method was used to investigate the active ingredients,targets and molecular mechanisms of THSWD in the intervention of IgAN fibrosis.On this basis,in vitro experiments were conducted to verify the effect of THSWD on the expression of ERK factor in BALB/c 3 T3 cells.The active ingredients and targets in THSWD were collected through the TCMSP.Sixty-one active ingredients and 240 targets including luteolin and quercetin were screened,and 185 targets were obtained by intersecting with CTD database to search IgAN related targets.Cytoscape software and STRING database were used to construct"THSWD-active ingredients-targets"network and protein-protein interaction network,and 69 core targets were screened.In DAVID′s GO enrichment analysis and KEGG pathway analysis of the core targets and cell experiments,the results showed that ERK was an important factor for THSWD to interfere with IgAN fibrosis,and THSWD intervention could significantly decrease cell activity,ERK1/2 mRNA expression,and p-ERK1/2 protein expression.This study preliminarily revealed that THSWD may delay the growth of fibroblasts by affecting ERK factor and its phosphorylation level.

关 键 词：IGAN 桃红四物汤 血瘀 网络药理学 ERK BALB/c 3T3细胞 

分 类 号：R285.5[医药卫生—中药学]