摘要
目的:利用网络药理学探讨防己黄芪汤治疗慢性心力衰竭(CHF)的潜在机制。方法:利用中药系统药理学技术平台(TCMSP)检索防己黄芪汤的药物活性成分及其相关靶点,并通过全球蛋白质资源(Uniprot)数据库进行基因的标准化处理。通过在线人类孟德尔遗传(OMIM)数据库、基因卡片(GeneCards)数据库检索得到CHF的相关靶点,将药物活性成分靶点与疾病的相关靶点相映射,取得的交集靶点即为防己黄芪汤治疗CHF的潜在靶点。利用Cytoscape软件构建防己黄芪汤治疗CHF的“药物-成分-疾病”靶点网络图,并运用生物分子功能注释系统(STRING)数据库以及Cytoscape软件构建防己黄芪汤治疗CHF的核心蛋白质互作(PPI)靶点网络图。利用DAVID数据库对获得的交集靶点进行基因本体论(GO)生物过程和京都基因与基因组百科全书(KEGG)通路富集分析。结果:筛选出的防己黄芪汤治疗CHF的活性成分有124个,相关靶点135个,与CHF相交合的靶点涉及α-1β肾上腺素受体(ADRA1B)和一氧化氮合酶3(NOS3)等。防己黄芪汤治疗CHF的GO生物过程涉及G蛋白偶联乙酰胆碱受体活性、药物结合、平滑肌收缩的正调控、对药物的反应等;防己黄芪汤治疗CHF可能与钙信号传导途径、神经活性配体-受体相互作用、环磷酸鸟苷酸/环磷酸鸟苷酸依赖的蛋白激酶(cGMP/PKG)信号通路、环磷酸腺苷(cAMP)信号通路、心肌细胞中的肾上腺素信号传导等通路相关。结论:防己黄芪汤治疗CHF涉及多个靶点、生物过程与通路,提示防己黄芪汤治疗CHF的机制较为复杂。
Objective:To explore the potential mechanism of Fangji Huangqi Decoction(防己黄芪汤)in treating chronic heart failure(CHF)by using network pharmacology.Methods:Using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the active components and related targets of Fangji Huangqi Decoction were searched,and the genes were standardized through the global protein resources(Uniprot)database.The related targets of CHF were obtained by searching online OMIM database and GeneCards database,and the targets of drug active ingredients were mapped with the related targets of diseases,and the obtained intersection targets were the potential targets of Fangji Huangqi Decoction in treating CHF.The target network diagram“drug-component-disease”of Fangji Huangqi Decoction in treating CHF was constructed by using Cytoscape software,and the core protein interaction(PPI)target network diagram of Fangji Huangqi Decoction in treating CHF was constructed by using biomolecule function annotation system(STRING)database and Cytoscape software.Using DAVID database,the genetic ontology(GO)biological process and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out.Results:There were 124 active ingredients of Fangji Huangqi Decoction in treating CHF,and 135 related targets.The targets that intersect with CHF involveα-1βadrenoceptor(ADRA1B)and nitric oxide synthase 3(NOS3).The GO biological process of Fangji Huangqi Decoction in treating CHF involves G protein-coupled acetylcholine receptor activity,drug binding,positive regulation of smooth muscle contraction,drug response,etc.The treatment of CHF with Fangji Huangqi Decoction might be related to calcium signaling pathway,neuroactive ligand-receptor interaction,cyclic guanosine monophosphate/cyclic guanosine monophosphate-dependent protein kinase(cGMP/PKG)signaling pathway,cAMP signaling pathway,adrenalin signaling pathway in myocardial cells,etc.Conclusion:The treatment of CHF with Fangji Huangqi Decoction involves multiple targets,biological processes and pathways,which shows that the mechanism of Fangji Huangqi Decoction in treating CHF is complicated.
作者
范吉林
朱婷婷
张世亮
FAN Jilin;ZHU Tingting;ZHANG Shiliang(Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China)
出处
《山东中医药大学学报》
2021年第3期340-346,共7页
Journal of Shandong University of Traditional Chinese Medicine
基金
国家科技重大专项重大新药创制项目(编号:2017ZX09301003)。
关键词
防己黄芪汤
慢性心力衰竭
网络药理学
药物活性成分靶点
蛋白质互作靶点
《金匮要略》
Fangji Huangqi Decoction
chronic heart failure
network pharmacology
targets of active pharmaceutical ingredients
protein interaction target
Synopsis of Golden Chamber
