摘要
目的 基于网络药理学方法分析丁香酚治疗心肌缺血再灌注损伤(MIRI)的作用靶点及相关通路。方法 将丁香酚“Eugenol”输入TCMSP数据库检索丁香酚作用靶点,将“Myocardial Ischemia Reperfusion Injury”输入GeneCards、OMIM数据库检索MIRI相关靶点;将两者交集后获得丁香酚-MIRI共同靶点,导入String数据库建立蛋白质互作网络(PPI)图,导入Cytoscape3.7.2软件进行聚类分析并寻找核心靶点;将丁香酚-MIRI共同靶点导入Matescape基因富集分析在线工具数据平台,进行GO功能和KEGG通路富集分析。结果 共得到不重复的丁香酚作用靶点100个、MIRI相关靶点1 085个、丁香酚-MIRI共同靶点33个。丁香酚-MIRI共同靶点的PPI图显示每个活性成分平均节点度7.09,PPI富集P值为1×10^(-16)。基于聚类分析的核心靶点筛选结果显示共得到2个基因簇和2个核心基因,核心基因分别为蛋白激酶B-α(Akt1)、血管内皮生长因子A(VEGFA)。丁香酚-MIRI共同靶点的GO生物功能富集分析结果显示,其主要涉及的生物学过程包括蛋白质磷酸化的正向调节、离子平衡、细胞迁移等,主要涉及的细胞成分包括突触后膜、膜筏、微膜区等,主要涉及的分子功能包括蛋白激酶活性、血红素结合、转录因子等。丁香酚-MIRI共同靶点的KEGG富集通路共有177条,主要包括晚期糖基化终末产物(AGE)—糖基化终末产物受体(RAGE)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、Toll样受体(TLR)信号通路等。结论 丁香酚治疗MIRI的核心靶点主要有Akt1、VEGFA,主要涉及AGE-RAGE、MAPK、TLR等相关通路。
Objective To explore the action targets and related pathways of eugenol in the treatment of myocardial ischemia-reperfusion injury(MIRI) based on network pharmacology.Methods "Eugenol" was input into TCMSP database to retrieve the action target,and "Myocardial Ischemia Reperfusion Injury" was input into Genecards and OMIM database to retrieve the relevant target of MIRI.After the intersection of the two,the Eugenol-MIRI common target was obtained,which was imported into the string database to establish the protein-protein interaction network(PPI) map,and then was imported into the Cytoscape 3.7.2 software for cluster analysis and search for the core target.Eugenol-MIRI common target was introduced into the Matescape gene enrichment analysis online tool data platform for GO function and KEGG pathway enrichment analysis.Results A total of 100 unrepeated eugenol action targets,1 085 MIRI-related targets and 33 Eugenol-MIRI common targets were obtained.The PPI diagram of Eugenol-MIRI intersection target showed that the average nodal degree of each active ingredient was 7.09,and the PPI enrichment p-value was 1×10^(-16).The screening results of core targets based on cluster analysis showed that a total of 2 gene clusters and 2 core genes were obtained,and the core genes were protein kinase B-α(AKT1) and vascular endothelial growth factor A(VEGFA).The results of GO biological function enrichment analysis of Eugenol MIRI common target showed that its main biological processes ineluded positive regulation of protein phosphorylation,ion balance,cell migration,etc.,the main cellular components included postsynaptic membrane,membrane raft,membrane microdomains,etc.,and the main molecular functions included protein kinase activity,heme binding,transcription factors,etc.There were 177 KEGG enrichment pathways of Eugenol-MIRI common target,mainly including advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE) signaling pathway,mitogen activated protein kinase(MAPK) signaling pathway,and toll-like receptor(TLR) signaling pathway,etc.Conclusion The core targets of eugenol in the treatment of MIRI mainly include Aktl and VEGFA,mainly involving AGE-RAGE,MAPK,TLR and other related pathways.
作者
韩运祺
石佳琦
朱秋梦
钱新宇
肖云峰
李文妍
HAN Yunqi;SHI Jiaqi;ZHU Qiumeng;QIAN Xinyu;XIAO Yunfeng;LI Wenyan(College of Pharmacy,Inner Mongolia Medical University,Huhehot 010110,China;不详)
出处
《山东医药》
CAS
2022年第23期15-18,共4页
Shandong Medical Journal
基金
内蒙古自治区自然科学基金面上项目(2020MS08117)
内蒙古医科大学科技百万工程联合项目[YKD2018KJBW(LH)057]。
