基于网络药理学、分子对接及实验验证探讨参附益心颗粒治疗心力衰竭的作用机制  

Exploring the Mechanism of Action of Shenfu Yixin Granules in the Treatment of Heart Failure Based on Network Pharmacology,Molecular Docking and Experimental Verification

作　　者：王彬[1] 王新陆[2] 李兰馨 张泸丹 乔利杰 卫靖靖 朱明军[2] WANG Bin;WANG Xinlu;LI Lanxin;ZHANG Ludan;QIAO Lijie;WEI Jingjing;ZHU Mingjun(Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China;Heart Center,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003 Henan,China)

机构地区：[1]河南中医药大学,河南郑州450046 [2]河南中医药大学第一附属医院心脏中心,河南郑州450003

出　　处：《中药新药与临床药理》2024年第9期1352-1363,共12页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(82004178,82030120);河南省科技攻关项目(232102310469)。

摘　　要：目的基于网络药理学、分子对接及实验验证探讨参附益心颗粒治疗心力衰竭的作用机制。方法(1)通过中药系统药理学数据库与分析平台(TCMSP)检索、筛选参附益心颗粒组方中药的有效活性成分;利用PubChem数据库、Swiss Target Prediction平台进行作用靶点预测;通过GeneCards、OMIM数据库检索、筛选心力衰竭疾病相关靶点;通过Venny 2.1.0平台对参附益心颗粒活性成分作用靶点与心力衰竭疾病相关靶点取交集(共同靶点),即为参附益心颗粒抗心力衰竭的潜在作用靶点。将潜在作用靶点导入STRING数据库,构建蛋白互作(PPI)网络,筛选参附益心颗粒治疗心力衰竭的核心靶点。通过Cytoscape 3.6.1软件构建“药物-活性成分-疾病-靶点”网络,筛选参附益心颗粒治疗心力衰竭的关键活性成分。利用DAVID数据库对潜在作用靶点进行GO功能及KEGG通路富集分析。利用AutoDock Vina软件对关键活性成分和核心靶点进行分子对接验证。(2)将SD大鼠随机分为假手术组、模型组、参附益心颗粒组(5.28 g·kg^(-1))及阳性药组(沙库巴曲缬沙坦组,20.8 mg·kg^(-1)),每组8只。采用结扎左冠状动脉前降支的方法复制急性心肌梗死后心力衰竭大鼠模型。灌胃给药,每日1次,连续4周。采用超声心动图检测大鼠心功能:左室射血分数(LVEF)、左室短轴缩短率(LVFS);HE、Masson染色法观察大鼠心脏组织病理变化;ELISA法检测血清脑钠素(BNP)、心钠肽(ANP)、醛固酮(ALD)水平;qPCR及Western Blot法检测心脏组织CAV1、F2、MAPK1 mRNA及蛋白表达水平。结果(1)共获得参附益心颗粒的活性成分210个,作用靶点1196个,心力衰竭疾病相关靶点801个;通过Venny 2.1.0平台取交集,共得到参附益心颗粒治疗心力衰竭的潜在作用靶点(共同靶点)97个。通过“药物-活性成分-疾病-靶点”网络分析得到槲皮素、木犀草素、花生四烯酸、山柰酚、丹参醛等关键活性成分。Objective This study aims to examine the potential mechanism of Shenfu Yixin Granules on heart failure(HF)based on network pharmacology,molecular docking,and experimental verification.Methods(1)The active components of herbs in Shenfu Yixin Granules were screened and retrieved through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).PubChem database and Swiss Target Prediction platform were used to predict targets.GeneCards and OMIM databases were used to screen HF-related targets.The intersection of active ingredient targets of Shenfu Yixin Granules and HF-related targets was performed by using Venny 2.1.0 platform to obtain common targets,which were the potential targets for anti-HF effect of Shenfu Yixin Granules.The potential targets were imported into the STRING database to construct a protein-protein interaction(PPI)network and screen the core targets of Shenfu Yixin Granules for the treatment of HF.GO functional and KEGG pathway enrichment analysis of potential targets were carried out by using DAVID database.AutoDock Vina software was used for molecular docking validation of key active ingredients and core targets.(2)SD rats were randomly allocated into sham operation group,model group,Shenfu Yixin Granules(5.28 g·kg^(-1))group,and positive control group(sacubitril-valsartan,20.8 mg·kg^(-1)),with eight rats in each group.A rat model of HF after myocardial infarction was established by ligating the left anterior descending coronary artery.The rats were subsequently administered orally with the corresponding drugs once daily for a period of four weeks.Cardiac function including left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)in rats was assessed by echocardiography.Additionally,the histopathological alterations in rat heart tissue were examined using hematoxylin-eosin(HE)staining and Masson staining.The serum levels of brain natriuretic peptide(BNP),artial natriuretic peptide(ANP),and aldosterone(ALD)were determined by enzyme

关 键 词：心力衰竭 参附益心颗粒 网络药理学 分子对接 实验验证 心肌纤维化 大鼠 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]