摘要
目的通过网络药理学方法研究植物雌激素类中药单体治疗心肌缺血再灌注损伤(MIRI)的作用机制和潜在靶点。方法通过检索PubMed、中国知网全文数据库(CNKI),在植物雌激素范畴内查找已通过实验验证的对心肌缺血再灌注损伤有积极干预作用的中药单体;通过PharmMapper数据库查询相关中药单体的靶点;利用GeneCard、OMIM数据库筛选疾病靶点;通过R语言绘制Venn图找到交集靶点;用Cytoscape 3.6.1软件绘制中药单体与交集靶点的网络图;用STRING数据库和Cytoscape 3.6.1绘制蛋白相互作用(PPI)网络图;利用R语言进行基因本体(GO)功能富集和京都基因和基因组百科全书(KEGG)信号通路分析。结果检索得到10个植物雌激素类中药单体,分别是染料木素、槲皮素、三七皂苷R1、白藜芦醇、葛根素、丹参酮ⅡA、人参皂苷Rb1、人参皂苷Rb3、人参皂苷Re、人参皂苷Rg1。获得中药单体靶点515个、疾病靶点1069个,通过Venn图得到交集靶点57个。PPI示核心靶点有血清清蛋白(ALB)、表皮生长因子受体(EGFR)、胱天蛋白酶3(CASP3)、丝裂原激活的蛋白激酶1(MAPK1)等12个,GO富集分析主要涉及与内肽酶活性、核受体活性、配体激活转录因子活性等生物过程有关,KEGG富集分析主要涉及雌激素信号通路、流体剪切应力和动脉粥样硬化、细胞凋亡、白细胞介素-17(IL-17)信号通路、血管内皮生长因子(VEGF)信号通路等。结论植物雌激素类中药单体作用机制可能是通过雌激素受体信号通路的两种途径以及其他信号通路多靶点、多通路地发挥抗心肌缺血再灌注损伤作用。可从该角度进行心肌缺血再灌注损伤的实验研究及临床用药提供思路与参考。
Objective To investigate the mechanism and potential targets of phytoestrogens monomers in the treatment of myocardial ischemia reperfusion injury(MIRI)by network pharmacology.Methods Traditional Chinese medicine(TCM)monomers with positive intervention effect on myocardial ischemia reperfusion injury that have been verified by experiments were searched in the category of phytoestrogens by searching PubMed and China national knowledge infrastructure(CNKI)database.PharmMapper database was used to query the target of related TCM monomers.GeneCard and OMIM databases were used to screen disease targets.Venn diagram was drawn by R language to find intersection target.Cytoscape 3.6.1 software was used to draw the network diagram of monomer and intersection target of TCM.PPI network map with STRING database were formed and Cytoscape 3.6.1.Gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway were analyzed using R language.Results Ten phytoestrogens of TCM monomers were retrieved,including genistein,quercetin,notoginsenoside R1,resveratrol,puerarin,tanshinoneⅡA,ginsenoside Rb1,ginsenoside Rb3,ginsenoside Re,ginsenoside Rg1.A total of 515 monomer targets and 1069 disease targets were obtained.Fifty-seven intersection targets were obtained by Venn diagram.PPI showed there were 12 core targets including epidermal growth factor receptor(EGFR),Caspase-3(CASP3),mitogen-activated protein kinase(MAPK)1,nitric oxide synthase 3(NOS3)and estrogen receptor 1(ESR1),etc.GO enrichment showed endopeptidase activity,nuclear receptor activity,and ligand activated transcription factor activity were the main related biological processes.KEGG results showed that estrogen signaling pathway,fluid shear stress,atherosclerosis,apoptosis,interleukin(IL)-17 signaling pathway,and vascular endothelial growth factor(VEGF)signaling pathway were involved.Conclusion The phytoestrogens monomers may be through two pathways of estrogen receptor signaling pathway and other signaling pathways that exert multi-target and multi-
作者
王禹萌
寿鑫甜
范宗静
崔杰
薛栋华
吴旸
WANG Yumeng;SHOU Xintian;FAN Zongjing;CUI Jie;XUE Donghua;WU Yang(Graduate School of Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital Beijing University of Chinese Medicine,Beijing 100078,China)
出处
《中西医结合心脑血管病杂志》
2022年第7期1153-1159,共7页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金项目(No.81573900)
北京中医药大学新奥奖励基金项目(No.2019-XAJLJJ-019)。
关键词
心肌缺血再灌注损伤
植物雌激素
网络药理学
作用机制
myocardial ischemia reperfusion injury
MIRI
phytoestrogens
network pharmacology
mechanism
