基于复方中药网络药理学和分子对接技术的芪苈强心胶囊治疗扩张型心肌病的药理机制及药效物质研究  

Pharmacological Mechanism and Pharmacoactive Substances of Qili Qiangxin Capsule for Treatment of Dilated Cardiomyopathy Based on Network Pharmacology and Molecular Complementing Technology of Traditional Chinese Medicine

作　　者：全无瑕 缪延栋 米登海[2,3] QUAN Wuxia;MIAO Yandong;MI Denghai(Yantai Affiliated Hospital of Binzhou Medical University,Yantai 264100,Shandong,China)

机构地区：[1]滨州医学院烟台附属医院,山东烟台264100 [2]兰州大学第一临床医学院,兰州730000 [3]甘肃省中医药研究院,兰州730000

出　　处：《中西医结合心脑血管病杂志》2023年第3期406-415,共10页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的:探究芪苈强心胶囊治疗扩张型心肌病的药理过程和分子机制。方法:通过中药系统药理学分析平台(TCMSP)检索芪苈强心胶囊中11味中药所含的化学成分及作用靶点。借助UniProt数据库查询靶点对应基因。通过基因名片数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、PharmGkb、治疗靶点数据库(TTD)以及DrugBank数据库筛选出扩张型心肌病的相关基因。采用Cytoscape软件构建“中药-活性成分-靶点”网络。通过CytoNCA插件筛选出核心基因,运用基因本体(GO)功能注释及京都基因和基因组百科全书(KEGG)通路分析明确靶点基因的功能及参与调控的信号转导通路。通过分子对接评价“中药-成分-靶点”网络中核心成分与JUN和TP53的结合作用。结果:芪苈强心胶囊“中药-成分-靶点”网络包含130个化合物和161个靶点,在蛋白质互作网络中共筛选出15个核心基因(JUN、TP53、STAT3、MAPK3、MAPK1、AKT1、FOS、EGFR、ESR1、CCND1、MAPK14、RELA、MAPK8、HIF1A、VEGFA)。靶点主要涉及有毒物质反应、脂多糖反应、营养水平反应、细胞外刺激反应、金属离子反应等与心肌细胞损伤相关的生物学过程;主要参与人巨细胞病毒感染、糖尿病并发症中的AGE-RAGE信号通路、流体剪应力与动脉粥样硬化等通路的调控,产生保护心肌细胞,减轻心室重构等作用,进而发挥改善心脏功能的功效。分子对接显示芪苈强心胶囊中核心成分与JUN和TP53的亲和作用较好。结论:芪苈强心胶囊可以通过多种活性成分作用于靶点基因调控相关信号转导通路,从而治疗扩张型心肌病。Objective:To explore the molecular mechanism of Qili Qiangxin Capsule for treatment of dilated cardiomyopathy.Methods:The chemical constituents and targets of 11 traditional Chinese medicines in Qiliqiangxin Capsule were analyzed by traditional Chinese medicine(TCM)system pharmacology database(TCMSP).The target corresponding gene was queried by Uni prot database.Genes related to dilated cardiomyopathy were screened through GeneCards,Online Mendelian Inheritance in Man(OMIM),PharmGkb,Therapeutic Target Database(TTD)and DrugBank databases.The network of"TCM-active ingredient-target"was constructed using Cytoscape software.The core genes were screened by CytoNCA plug-in,and the functions of target genes and signal transduction pathways involved in regulation were identified by gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking was performed to evaluate the binding effect of core components in the"medicine-component-target"network with JUN and TP53.Results:Qili Qiangxin Capsule"medicine-ingredient-target"network contained 130 compounds and 161 targets.A total of 15 core genes(JUN,TP53,STAT3,MAPK3,MAPK1,AKT1,FOS,EGFR,ESR1,CCND1,MAPK14,RELA,MAPK8,HIF1A,VEGFA)were screened out in the protein interaction network.The targets mainly involved toxic substances reaction,lipopolysaccharide reaction,nutrient level reaction,extracellular stimulus reaction,metal ion reaction and other biological processes related to myocardial cell injury.It was mainly involved in the regulation of AGE-RAGE signaling pathway in human cytomegalovirus infection,diabetes complications,fluid shear stress,and atherosclerosis,which could protect cardiomyocytes and reduce ventricular remodeling,thus improving cardiac function.Molecular alignment indicated that the core components of Qili Qiangxin Capsule showed better affinity with JUN and TP53.Conclusion:Qili Qiangxin Capsule can treat dilated cardiomyopathy through a variety of active ingredients on target gene regulated signal tr

关 键 词：扩张型心肌病 芪苈强心胶囊 网络药理学 中药 分子对接 

分 类 号：R285[医药卫生—中药学]