基于网络药理学探讨加味苏叶黄连汤治疗慢性肾衰竭的作用机制  

Mechanism of the modified Suye Huanglian decoction in treating chronic renal failure based on network pharmacology

作　　者：冯修承 肖振卫[1] FENG Xiucheng;XIAO Zhenwei

机构地区：[1]山东中医药大学,山东济南250014

出　　处：《中医临床研究》2021年第33期83-90,共8页Clinical Journal Of Chinese Medicine

摘　　要：目的:采用网络药理学的方法探讨加味苏叶黄连汤治疗慢性肾衰竭的作用机制。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,TCSMP)和中医药综合数据库(Traditional Chinese Medicine Integrated Database,TCMID)平台筛选加味苏叶黄连汤的有效成分,TCMSP及STITCH数据库筛选药物作用靶点,使用DisGeNET和DrugBank检索慢性肾衰竭疾病靶点。获取药物-疾病靶点交集,使用STRING数据库制作靶点间相互作用网络,筛选置信度高的靶点及成分,运用DAVID数据库进行基因本体论(Gene Ontology,GO)富集和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析,使用Cytoscape软件构建成分-靶点-通路网络,并进行拓扑分析。结果:得到置信度高的加味苏叶黄连汤涉及慢性肾衰竭的靶点27个,共同靶点富集有KEGG通路15条,生物过程102条,分子功能8条,细胞组成12条。拓扑网络分析后得到转化生长因子-β1(Transforming Growth Factor-β1,TGF-β1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-6(Interleukin-6,IL-6)、转录因子AP-1(Jun ProtoOncogene,JUN)、内皮型一氧化氮合酶(Nitric Oxide Synthase 3,NOS3)、前列腺素G/H合酶1(Prostaglandin-Endoperoxide Synthase1,PTGS1)、前列腺素G/H合酶2(Prostaglandin-Endoperoxide Synthase2, PTGS2)、转录因子p65(RELA ProtoOncogene, NF-κB Subunit,RELA)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)等9个关键靶点,及槲皮素(Quercetin)、柚皮素(Naringenin)、木犀草素(Luteolin)、川陈皮素(Nobiletin)等4个关键成分。结论:加味苏叶黄连汤可能通过改变TGF-β1、TNF、IL-6、JUN、NOS3、PTGS1、PTGS2、RELA等靶点表达,调控TNF信号通路、核因子-κB(Nuclear Factor-κB,NF-κB)信号通路、缺氧诱导因子1(Hypoxia Inducible Factor 1,HIF-1)信号通路、Nod样受体信号通路、T细胞受体信号通路、Toll样�Objective:To study the mechanism of the modified Suye Huanglian decoction(加味苏叶黄连汤)on chronic renal failure.Methods:TCMSP and TCMID data platform were used to obtain the effective components of the modified Suye Huanglian decoction,TCMSP and STITCH database were used to obtain drug target,and disease target of chronic renal failure was searched through DisGeNET and DrugBank databases to obtain relevant intersection,target interaction network was made with STRING database,targets were obtained by setting confidence,KEGG and GO pathway enrichment analysis were conducted by DAVID website,and component-target-pathway network was constructed by Cytoscape software.Results:27 targets of the modified Suye Huanglian decoction involving chronic renal failure were obtained,15 KEGG pathway and 102 biological processes,8 molecular functions and 12 cell components were screened.After topological network analysis,9 key targets,including TGF-β1,TNF,IL-6,JUN,NOS3,PTGS1,PTGS2,RELA,VEGFA,and 4 key components,including Quercetin,Naringe,Luteolin and Nobiletin were obtained.Conclusion:The modified Suye Huanglian decoction may change the expression of TGF-β1,TNF,IL-6,JUN,NOS3,PTGS1,PTGS2,RELA targets,regulate TNF signaling pathway,NF-kappa B signaling pathway,HIF-1 signaling pathway,NOD-like receptor signaling pathway,T cell receptor signaling pathway and Toll-like receptor signaling pathway,mediate immune response and inflammatory response in vivo,decrease the levels of inflammatory factors and growth factors in serum,and then reduce the degeneration and necrosis of renal tubular epithelial cell to delay glomerulosclerosis and interstitial fibrosis.It provides a reference and theoretical basis for the further experimental research of the prescription.

关 键 词：加味苏叶黄连汤 慢性肾衰竭 网络药理学 

分 类 号：R692.5[医药卫生—泌尿科学]