基于网络药理学、分子对接探讨强心汤治疗慢性心力衰竭的潜在作用机制  

Potential Mechanism of Action of Qiangxin Decoction(强心汤)for Chronic Heart Failure Based on Network Pharmacology and Molecular Docking

作　　者：毛美玲 卢健棋 谢丽钰 庞延 张鼎 石炜琦 刘水花 蔡宗余 张诗雨 黄敏[1] MAO Meiling;LU Jianqi;XIE Liyu;PANG Yan;ZHANG Ding;SHI Weiqi;LIU Shuihua;CAI Zongyu;ZHANG Shiyu;HUANG Min(Guangxi University of Chinese Medicine,Nanning,530200;The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine)

机构地区：[1]广西中医药大学,广西壮族自治区530200 [2]广西中医药大学第一附属医院

出　　处：《中医杂志》2023年第20期2132-2137,共6页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82160887,81673891);广西自然科学基金(2021GXNSFAA220111,2021GXNSFBA196018);广西中医药大学2023年研究生教育创新计划(YCBXJ2023024)。

摘　　要：目的基于网络药理学、分子对接的方式揭示强心汤治疗慢性心力衰竭的作用靶点和分子机制。方法从TCMSP数据库检索强心汤的活性成分,应用GeneCards、OMIM、TTD、PharmGkb、DrugBank数据库筛选慢性心力衰竭靶点,取交集获得强心汤治疗慢性心力衰竭的交集靶点。采用STRING平台构建蛋白互作网络(PPI),Cytoscape 3.8.0软件网络拓扑计算筛选核心靶点,R 4.2.3进行GO富集分析及KEGG通路富集分析,构建“活性成分-靶点”网络。采用AutoDock 1.5.7进行分子对接预测活性成分和核心靶点的结合性能。结果筛选出强心汤治疗慢性心力衰竭的交集靶点75个,其中核心靶点为雌激素受体1(ESR1,度值=7)、核受体辅激活因子1(NCOA1,度值=8)、糖皮质激素受体(NR3C1,度值=7)、核受体辅激活因子2(NCOA2,度值=7)。GO富集分析结果显示,分子功能中P值最小的前3项有G蛋白偶联胺受体活性、突触后神经递质受体活性、神经递质受体活性(P<0.01);生物过程中P值最小的前3项有腺苷酸环化酶激活肾上腺素受体信号通路、肾上腺素受体信号通路、腺苷酸环化酶调节G蛋白偶联受体信号通路(P<0.01);细胞组成中P值最小的前3项为突触后膜、突触膜、突触前膜的组成部分(P<0.01)。KEGG富集分析显示,关键信号通路前5位的为神经活性配体-受体的相互作用、钙信号通路、多巴胺能突触、可卡因成瘾、环状磷酸鸟苷-蛋白激酶G(cGMP-PKG)信号通路。分子对接结果显示,木犀草素、异黄酮与4个核心靶点(ESR1、NCOA1、NR3C1、NCOA2)的结合能更低,结构更稳定。结论强心汤治疗慢性心力衰竭与神经活性配体-受体的相互作用、钙信号通路、多巴胺能突触、化学致癌-受体激活、cGMP-PKG信号通路、脂质和动脉粥样硬化、cAMP信号通路等通路相关,木犀草素、异黄酮可能是其治疗慢性心力衰竭的核心活性化合物。Objective To reveal the targets and molecular mechanisms of the action of Qiangxin Decoction(强心汤)for the treatment of chronic heart failure based on the combination of network pharmacology and molecular dock⁃ing.Methods The active ingredients of Qiangxin Decoction were retrieved from TCMSP database,and the targets of chronic heart failure were screened by searching GeneCards,OMIM,TTD,PharmGkb,and DrugBank databases,and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure.STRING platform was used to construct the protein-protein interaction network(PPI),Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets,and R 4.2.3 was used to construct the“active ingredient-target”network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis.AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets.Results Seventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction,among which the core targets were estrogen receptor 1(ESR1,degree value=7),nuclear receptor coactivator 1(NCOA1,degree value=8),glucocorticoid receptor(NR3C1,degree value=7),and nuclear receptor coactivator 2(NCOA2,degree value=7).GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity,postsynaptic neurotransmitter receptor activity,and neurotransmitter receptor activity(P<0.01);the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway,adrenergic receptor signaling pathway,and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway(P<0.01);the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane,synaptic membrane,and presynaptic mem⁃brane(P<0.01).KEGG enrichment ana

关 键 词：慢性心力衰竭 强心汤 网络药理学 分子对接 核心靶点 

分 类 号：R285[医药卫生—中药学]