基于网络药理学和分子对接法分析5种中药活性成分治疗心肌缺血再灌注损伤的机制  

Mechanism of Five TCM Active Ingredients in Treatment of Myocardial Ischemia-Reperfusion Injury Analyzed by Network Pharmacology and Molecular Docking Method

作　　者：戎嘉诚 洪俊 黄磊 陈旭东 RONG Jiacheng;HONG Jun;HUANG Lei;CHEN Xudong(Ningbo Hangzhou Bay Hospital,Ningbo 315000,Zhejiang,China)

机构地区：[1]宁波市杭州湾医院,浙江宁波315000

出　　处：《辽宁中医杂志》2024年第6期5-10,I0003-I0005,共9页Liaoning Journal of Traditional Chinese Medicine

基　　金：浙江省卫生健康科技计划项目面上项目(2021KY1072)。

摘　　要：目的利用网络药理学和分子对接法的分析技术,预测大黄素、木香烃内酯、水甘草碱、表儿茶素没食子酸酯、冬凌草甲素等中药活性成分治疗心肌缺血再灌注损伤的作用机制。方法使用中药系统药理数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、HERB和SwissTargetPrediction数据库寻找5种药物活性成分的作用靶点,并通过Genecards数据库寻找心肌缺血再灌注损伤的疾病靶点,两组靶点相交得到5种活性成分针对于心肌缺血再灌注损伤的潜在治疗靶点组合。接着对上述靶点合集进行功能富集(采用R语言程序,“ClusterProfiler”包),并进一步分析,随后构建活性成分、靶点、通路、疾病和富集结果间的多种关系网络,使用Cytoscape进行美化。使用String数据库和Cytoscape软件构建靶点蛋白互作网络(protein-protein interaction networks,PPI)集合,并利用Cytoscape的CytoHubba功能筛选关键(hub)靶基因。使用PyMOL和Autodock软件进行分子对接和结果可视化及美化。结果5种活性成分治疗心肌缺血再灌注损伤的潜在作用靶点共有51个,我们发现在整体的蛋白互作网络中排名前5位的关键基因分别为编码丝氨酸/苏氨酸蛋白激酶1(Akt serine/threonine kinase 1,AKT1)、白细胞介素1β(interleukin-1β,IL-1β)、半胱天冬酶3(Caspase 3,CASP3)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、信号转导子和转录激活子3(signal transolucer and activator of transcription 3,STAT3),它们涉及基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)相关富集通路74条、基因本体论(gene ontology,GO)生物过程富集条目1007条、GO细胞功能富集条目39条。随后的分子对接结果发现,这5种活性成分各自与关键基因中的一种或多种结合较好。结论大黄素、木香烃内酯、水甘草碱、表儿茶素没食子酸酯、冬凌草甲素5种中草药�Objective To predict the mechanism of five active ingredients of Chinese herbal medicine emodin/costunolide/tabersonine/(-)-Epicatechin gallate/oridonin in the treatment of myocardial ischemia-reperfusion injury by using network pharmacology and molecular docking method.Methods The target of five active ingredients was obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),HERB and SwissTargetPrediction database,and the disease target of myocardial ischemia-reperfusion injury was obtained by Genecards database,and the target of five active ingredients for the treatment of myocardial ischemia-reperfusion injury was obtained by intersection of the two results above.The functional enrichment analysis of targets was conducted using the“ClusterProfiler”package of R software,and Cytoscape was adopted to construct multiple relationship networks among active ingredients,targets,pathways,diseases and enrichment results.The target protein interaction network was constructed using the String database and“Cytoscape”software,and key target genes were screened using“CytoHubba”function of Cytoscape.PyMOL and Autodock were used for molecular docking,visualization and beautification of the results.Results There were totally 51 potential targets of these five active ingredients in the treatment of myocardial ischemia-reperfusion injury.The top 5 key genes in the protein interaction network were AKT serine/threonine kinase 1(AKT1),interleukein-1β(IL-1β),Caspase 3(CASP3),vascular endothelial growth factor A(VEGFA)and signal transducer and activator of transcription 3(STAT3).There were 74 enrichment pathways related to Kyoto encyclopedia of genes and genomes(KEGG),1007 enrichment entries of gene ontology(GO)biological processes,and 39 enrichment entries of GO cell function.The results of molecular docking showed that each of the five active ingredients was well bound to one or more of the key genes.Conclusion Emodin/costunolide/tabersonine/(-)-epicatechin gallate/oridonin may

关 键 词：中草药 大黄素 木香烃内酯 水甘草碱 表儿茶素没食子酸酯 冬凌草甲素 心肌缺血再灌注损伤 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]