基于网络药理学研究扶正化瘀降浊通络方治疗慢性肾衰竭的作用机制  

Study on the Mechanism of Formula for Reinforcing Healthy Qi and Resolving Stasis and Suppressing Turbidity and Dredging Collaterals in Treating Chronic Renal Failure Based on Network Pharmacology

作　　者：何剑川 付饶 邹小康 陈明[2] HE Jianchuan;FU Rao;ZOU Xiaokang;CHEN Ming(Sichuan Integrative Medicine Hospital,Chengdu,Sichuan,China,610041;Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan,China,610072)

机构地区：[1]四川省中西医结合医院,四川成都610041 [2]成都中医药大学附属医院,四川成都610072

出　　处：《河南中医》2023年第8期1175-1183,共9页Henan Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81973673)。

摘　　要：目的:通过网络药理学方法研究扶正化瘀降浊通络方治疗慢性肾衰竭(chronic renal failure,CRF)的药效成分、作用靶点及信号通路,拟阐明其作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)等数据库和文献挖掘获取扶正化瘀降浊通络方组方中药的活性成分,利用Pharmmapper筛选化学成分潜在靶点;在GeneCards数据库、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)检索CRF相关靶点。将扶正化瘀降浊通络方活性成分相关靶点与CRF靶点上传Venny 2.1.0平台进行映射,交集靶点即为扶正化瘀降浊通络方治疗CRF的潜在靶点,并绘制靶点韦恩图。将潜在靶点导入STRING数据库构建蛋白互作(protein-protein interaction,PPI)网络并分析。使用Cytoscape等软件构建“药物-成分-靶点”网络并筛选核心成分。借助DAVID数据库对靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。利用Cytoscape 3.7.2软件构建“信号通路-靶点”网络及“药物-核心成分-核心靶点-信号通路”网络。结果:通过TCMSP数据库筛选得到316个活性成分及相关靶点2263个,通过Genecards、OMIM获得7806个CRF靶点,将二者进行映射筛选出潜在靶点635个。PPI网络分析筛选得到20个核心靶点。GO富集分析共涉及506个条目,包含分子功能98项,细胞成分50项,生物过程358项。KEGG富集分析得到105条信号通路。结论:蒽醌类、黄酮类等成分可能是关键药效成分,可通过调节磷脂酰肌醇3-激酶(phosphatidylinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、转化生长因子-β(transforming growth factor-β,TGF-β)等通路减Objective:To study the pharmacological components,targets,and signaling pathways of Formula for Reinforcing Healthy Qi and Resolving Stasis and Suppressing Turbidity and Dredging Collaterals in the treatment of chronic renal failure(CRF)through net⁃work pharmacology methods,and to elucidate its mechanism of action.Methods:Traditional Chinese medicine systems pharmacology da⁃tabase and analysis platform(TCMSP)and other databases and literature mining were used to obtain the active components of Formula for Reinforcing Healthy Qi and Resolving Stasis and Suppressing Turbidity and Dredging Collaterals,and Pharmmapper was used to screen the potential targets of chemical components.CRF⁃related targets were searched in GeneCards database and online mendelian in⁃heritance in man(OMIM)database.Targets related to the active components of Formula for Reinforcing Healthy Qi and Resolving Sta⁃sis and Suppressing Turbidity and Dredging Collaterals and CRF targets were uploaded to Venny 2.1.0 platform for mapping.The inter⁃section targets were the potential targets of the formula for the treatment of CRF,and the target Wayne diagram was drawn.Potential tar⁃gets were imported into STRING database to construct protein⁃protein interaction(PPI)network and analyzed.Softwares such as Cyto⁃scape were used to establish"drug⁃component⁃target"network and screen for core ingredients.The DAVID database was used for gene ontology(GO)function enrichment analysis and kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment a⁃nalysis.Cytoscape 3.7.2 software was used to construct the"signaling pathway⁃target"network and the"drug⁃core components⁃core target⁃signaling pathway"network.Results:A total of 316 active components and 2263 related targets were screened by TCMSP data⁃base,7806 CRF targets were obtained by Genecards and OMIM,and 635 potential targets were screened by mapping between them.PPI network analysis screened 20 core targets.A total of 506 items were involved in GO enrichment an

关 键 词：扶正化瘀降浊通络方 慢性肾衰竭 网络药理学 作用机制 

分 类 号：R285[医药卫生—中药学]