基于网络药理学探讨心衰合剂治疗心力衰竭的分子机制  

Mechanism of Xinshuaiheji in the treatment of heart failure based on network pharmacology

作　　者：杨琳[1] 王振裕[2] 范德宇 郑珺 孟袁 赵佳峪 YANG Lin;WANG Zhenyu;FAN Deyu;ZHENG Jun;MENG Yuan;ZHAO Jiayu(Beijing University of Traditional Chinese Medicine,Beijing 100029;Department of Health Care for Cadres,Beijing Hospital of Traditional Chinese Medicine,Beijing 100010)

机构地区：[1]北京中医药大学,北京100029 [2]首都医科大学附属北京中医医院干部保健科,北京100010

出　　处：《河北中医》2022年第10期1727-1735,共9页Hebei Journal of Traditional Chinese Medicine

摘　　要：目的基于网络药理学探讨心衰合剂治疗心力衰竭的分子作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)收集心衰合剂中药物的活性成分并筛选出相对应的靶点;通过GeneCards、DrugBank、OMIM、PharmGKB及TTD数据库获取心力衰竭疾病靶点;通过R语言4.04软件获得候选治疗靶点,通过Cytoscape 3.7.2软件构建“药物-有效成分-疾病靶点”网络,通过基因间功能关联关系数据库(STRING)对侯选治疗靶点进行蛋白质-蛋白质相互作用PPI(网络)分析,再利用Cytoscape的CytoHubba插件筛选得到核心治疗靶点;通过R语言4.04软件对候选治疗靶点进行基因本体(GO)功能富集分析与京都基因与基因组百科全书(KEGG)通路富集分析;最后使用Vina 1.1.2软件分析核心治疗靶点与其对应的药物活性成分进行分子对接。结果共得到心衰合剂活性成分216个、潜在作用靶点284个,心力衰竭靶点11215个,候选治疗靶点255个,并筛选得到7个关键成分,核心治疗靶点15个,GO功能富集分析条目2874个,KEGG通路富集分析通路175条。心衰合剂治疗心力衰竭主要成分为常春藤皂苷元、山奈酚、槲皮素等,核心治疗靶点为肿瘤坏死因子(TNF)、白细胞介素6(IL-6)、肿瘤蛋白p53(TP53)等,主要涉及脂质和动脉粥样硬化信号通路、磷脂酰肌酶3-激酶/蛋白激酶B(PI3K/Akt)信号通路、流体剪切应力与动脉粥样硬化信号通路等信号通路等,主要涉及药物反应、对脂多糖抗氧化反应等生物学过程,膜筏、膜微结构域、膜区等是参与反应的主要细胞组分,分子功能主要包括细胞因子受体结合、细胞因子活性、受体配体活动等。分子对接得到3组结合能最小的组合是转录因子p65(RELA)与黄芩素结构(最低结合能-9.4 kcal/mol)、FOS与黄芩素结构(最低结合能-9.6 kcal/mol)、FOS与汉防己甲素结构(最低结合能-9.7 kcal/mol),表明这些核心治疗靶点与其对应的药物活性成Objective To study the molecular mechanism of Xinshuaiheji in preventing and treating heart failure by network pharmacology.Methods The bioactive components of Xinshuaiheji were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the corresponding targets were screened.Genes related to the treatment of heart failure were obtained from GeneCards,DrugBank,OMIM,PharmGkb and TTD databases.The intersection of disease-related genes and compound corresponding targets was obtained by R software,and the network of targeted pathways was constructed by Cytoscape.The protein interaction network was analyzed by Interacting Genes(STRING)database,and the key therapeutic targets were screened by cytoHubba plug-in of Cytoscape.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets were performed by R software.Finally,Vina 1.1.2 was used to analyze the molecular docking sites of key therapeutic targets and their corresponding drug compounds.Results A total of 216 active ingredients of Xinshuaiheji,284 drug targets and 11215 targets of heart failure were obtained.Finally,255 key targets,2874 enriched targets by GO functional enrichment analysis and 175 enriched pathways by KEGG pathway enrichment analysis were obtained.The main components of Xinshuaiheji responsible for the treatment of heart failure included hederagenin,kaempferol,quercetin,apigenin,isorhamnetin,catechin,baicalein,etc.The key targets were TNF,IL6,TP53,ESR,RELA,etc.Key biological processes and pathways included lipid and atherosclerotic signaling pathway,PI3K?Akt signaling pathway,fluid shear stress and atherosclerotic signaling pathways.Enriched biological processes included drug reaction and antioxidant reaction to lipopolysaccharide.Membrane rafts,membrane microstructure domains,and membrane regions were the main cell components.Molecular functions mainly included cytokine receptor binding,cytokine activity,receptor ligand activity,etc.Molecular docking obtained th

关 键 词：心力衰竭 中药药理学 中药疗法 

分 类 号：R285.6[医药卫生—中药学]