心肌缺血预适应大鼠循环血微囊泡中miRNAs 表达谱分析

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。

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

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.