心肌缺血预适应大鼠循环血微囊泡中miRNAs表达谱分析  

Expression profiling of circulating microvesicles miRNAs derived from myocardial ischemic preconditioning in rats

作　　者：赵俊玉 祝倩 尚曼 李烨仪 刘淼 王艺璐 吴艳娜 刘艳霞 宋君秋 ZHAO Jun-yu;ZHU Qian;SHANG Man;LI Ye-yi;LIU Miao;WANG Yi-lu;WU Yan-na;LIU Yan-xia;SONG Jun-qiu(Department of Pharmacology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学基础医学院药理学系,天津300070

出　　处：《天津医科大学学报》2022年第3期235-241,共7页Journal of Tianjin Medical University

基　　金：天津市高等学校科技发展基金计划项目(20110106);高校博士学科专项科研基金(2010120211005);天津市自然科学基金(11JCZDJC18300)。

摘　　要：目的:分离提取心肌缺血预适应(IPC)模型大鼠循环血中的细胞微囊泡(MVs),探究IPC处理对循环血MVs中microRNAs(miRNAs)表达的影响。方法:健康雄性Wistar大鼠8只,随机分为IPC-MVs组和假手术对照(Sham-MVs)组,每组4只。建立大鼠心肌IPC模型,提取循环血IPC-MVs,采用Microarray分析两组循环血MVs中的miRNAs,利用生物信息学进行靶基因预测及功能分析。结果:与Sham-MVs组比较,IPC-MVs组中循环血差异表达显著上调的miRNAs共3个(P<0.01,FER<0.05):miR-1-3p、miR-133a-3p和miR-133b-3p(t=3.194、3.002、3.389,均P<0.05)。基因本体研究会数据库(GO)和京都基因与基因组百科全书(KEGG)分析显示,这些miRNAs可能通过调节心肌细胞中丝裂原活化蛋白激酶(MAPK)信号通路和Ras信号通路,发挥抗心肌缺血/再灌注(I/R)损伤的保护作用,可能参与调控的核心靶基因包括Ntrk2、Igf1、Gnai3和Bcl2l1。结论:IPC处理可使大鼠循环血MVs中miR-1-3p、miR-133a-3p和miR-133b-3p表达显著上调。Objective:To isolate and extract the cellular microvesicles(MVs)derived from the circulating blood of myocardial ischemic preconditioning(IPC)in rats,and analyze the effect of IPC treatment on microRNA(miRNAs)expression in circulating MVs.Methods:Eight healthy male Wistar rats were randomly divided into IPC-MVs group and sham-MVs group,with 4 rats in each group.IPC model was established in rats,IPC-MVs were isolated by ultracentrifugation from the peripheral blood.The miRNAs in the two groups of circulating MVs were analyzed using Microarray,then target genes were predicted and functional analysis was performed through bioinformatics.Results:There were 3 miRNAs up-regulated significantly in IPC-MVs compared with Sham-MVs(P<0.01,FER<0.05):miR-1-3p,miR-133a-3p and miR-133b-3p(t=3.194,3.002,3.389,all P<0.05).Gene Ontology Research Association Database(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that these miRNAs might play a protective role against myocardial ischemia/reperfusion(I/R)injury by regulating mitogen-activated protein kinase(MAPK)signaling pathway and Ras signaling pathway in cardiomyocytes.The core target genes that may be involved in the regulation including Ntrk2,Igf1,Gnai3 and Bcl2l1.Conclusion:The expressions of miR-1-3p,miR-133a-3p and miR-133b-3p in circulating MVs are upregulated significantly when treated with IPC in rats.

关 键 词：微囊泡 缺血预适应 MIRNAS 差异表达 

分 类 号：R54[医药卫生—心血管疾病]