Ischemic stroke is a serious disease with limited prevention methods, and various genes and microRNAs (miRNAs) have been found to be dysregulated in the pathogenesis of this disease. This study aims to explore the potential role of miR-381-3p in ischemic stroke, along with its underlying mechanism. A mouse model of ischemic stroke was developed using middle cerebral artery occlusion. Next, the expression of mitogen-activated protein kinase kinase kinase 8 (Map3k8) and CCAAT enhancer binding protein beta (Cebpb) was determined by RT-qPCR. Gain- and loss-of-function approaches were applied to analyze the effects of miR-381-3p, Cebpb and Map3k8 on the biological functions of endothelial progenitor cells (EPCs) with the involvement of the tumor necrosis factor-α (TNF-α) signaling pathway. In addition, dual luciferase reporter gene assay was performed for the analysis of the relationship among miR-381-3p, Map3k8 and Cebpb. Further, rescue experiment was performed with the help of JNK/p38 specific agonist, Anisomycin. Map3k8 and Cebpb were highly expressed in ischemic stroke. Loss-of-function of Map3k8 or Cebpb in EPCs contributed to accelerated proliferation, migration and angiogenesis of EPCs. Next, miR-381-3p downregulated the expression of its two target genes, Map3k8 and Cebpb. miR-381-3p overexpression promoted angiogenesis of EPCs, and inhibited inflammation, which could be reversed by restoration of Map3k8 or Cebpb. Additionally, silencing Map3k8 or Cebpb inhibited the activation of TNF-α signaling pathway. Furthermore, Anisomycin treatment could enhance inflammation and inhibit angiogenesis. Taken together, miR-381-3p downregulates Map3k8 and Cebpb to protect against ischemic stroke, broadening our understanding of the pathogenesis of ischemic stroke.

中文翻译：

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microRNA-381-3p通过抑制Cebpb和Map3k8促进血管生成和抑制炎症，从而预防缺血性中风。

缺血性中风是一种严重的疾病，其预防方法有限，并且已发现各种基因和微小RNA（miRNA）在该疾病的发病机理中失调。这项研究旨在探讨miR-381-3p在缺血性中风中的潜在作用及其潜在机制。使用大脑中动脉闭塞建立了缺血性中风的小鼠模型。接下来，通过RT-qPCR确定促分裂原活化的蛋白激酶激酶激酶8（Map3k8）和CCAAT增强子结合蛋白β（Cebpb）的表达。使用功能获得和丧失功能的方法来分析miR-381-3p，Cebpb和Map3k8对肿瘤坏死因子-α（TNF-α）参与的内皮祖细胞（EPC）生物学功能的影响）信号通路。此外，进行了双重荧光素酶报告基因分析，用于分析miR-381-3p，Map3k8和Cebpb之间的关系。此外，借助JNK / p38特异性激动剂Anisomycin进行了抢救实验。Map3k8和Cebpb在缺血性中风中高表达。EPC中Map3k8或Cebpb的功能丧失促进了EPC的增殖，迁移和血管生成。接下来，miR-381-3p下调了其两个靶基因Map3k8和Cebpb的表达。miR-381-3p过表达促进EPC的血管生成，并抑制炎症，这可以通过恢复Map3k8或Cebpb来逆转。此外，沉默Map3k8或Cebpb抑制TNF-α信号通路的激活。此外，茴香霉素治疗可增强炎症并抑制血管生成。在一起