过表达miR-101抑制JAK2/STAT3信号通路减缓急性心肌梗死模型大鼠心室重构

doi:10.16352/j.issn.1001-6325.2025.03.0281

摘要/Abstract

摘要： 目的探究miR-101对急性心肌梗死(AMI)后大鼠心室重构的影响和分子作用机制。方法采用结扎冠脉左前降支法构建AMI大鼠模型。将AMI大鼠分为AMI组、agomir-NC组、miR-101 agomir组和coumermycin A1组,另设置假手术组,每组12只。TargetScan 8.0数据库和双荧光素酶报告基因实验分析miR-101与JAK2靶向关系。RT-qPCR检测心肌组织miR-101表达。超声检测大鼠LVESD、LVEDD、LVEF和LVFS。ELISA检测血清中IL-1β、IL-6和TNF-α含量。HE染色检测心肌组织病变,Masson染色检测心肌组织纤维化。免疫组织化学染色检测心肌组织中collagenⅠ和TGF-β表达。Western blot检测E-cadherin、N-cadherin、vimentin、p-JAK2、JAK2、p-STAT3和STAT3蛋白表达。结果与AMI组和agomir-NC组比较,miR-101 agomir组大鼠心肌组织病变和相对纤维化面积均降低(P＜0.05), LVESD、LVEDD、L-1β、IL-6、TNF-α、collagen Ⅰ、TGF-β、N-cadherin、vimentin、p-JAK2和p-STAT3水平均降低(P＜0.05), miR-101、LVEF、LVFS和E-cadherin水平均升高(P＜0.05)。相较于miR-101 agomir组,coumermycin A1组大鼠心肌组织相对纤维化面积和病变程度均升高(P＜0.05), LVESD、LVEDD、L-1β、IL-6、TNF-α、collagenⅠ、TGF-β、N-cadherin、vimentin、p-JAK2和p-STAT3水平均升高(P＜0.05), miR-101、LVEF、LVFS和E-cadherin水平均降低(P＜0.05)。结论 miR-101通过靶向JAK2/STAT3信号通路,抑制AMI后心肌组织炎性病变、心肌纤维化和上皮细胞-间充质转化(EMT)过程,进而缓解AMI后大鼠心室重构。

关键词: miR-101, JAK2/STAT3信号通路, 急性心肌梗死, 心室重构, 心肌纤维化

Abstract: Objective To explore the effect and underlying molecular mechanism of miR-101 on ventricular remodeling in rats after acute myocardial infarction (AMI). Methods The AMI rat model was established using the left anterior descending coronary artery ligation method. The AMI rats were randomly divided into AMI group, agomir-NC group, miR-101 agomir group and coumermycin A1 group, another 12 rats were selected as sham group with 12in each . The targeting relationship between miR-101 and JAK2 was analyzed by Target Scan 8.0 database and double luciferase reporter gene assay. The expression of miR-101 in rat myocardium was detected by RT-qPCR. LVESD, LVEDD, LVEF and LVFS were measured by ultrasonography. The level of IL-1β, IL-6 and TNF-α in rats serum was determined by ELISA. The myocardial tissue lesion and fibrosis were detected by HE staining and Masson staining. The expression of collagenⅠ and TGF-β in rat myocardial tissue was detected by immunohistochemical staining. The expression of E-cadherin, N-cadherin, Vimentin, p-JAK2, JAK2, p-STAT3 and STAT3 proteins was detected by Western blot. Results Compared with AMI group and agomir-NC group, the myocardial tissue lesions and fibrotic area in miR-101 agomir group were significantly decreased(P＜0.05), the level of LVESD, LVEDD, L-1β, IL-6, TNF-α, collagenⅠ, TGF-β, N-cadherin, vimentin, p-JAK2 and p-STAT3 decreased (P＜0.05). The levels of miR-101, LVEF, LVFS and E-cadherin were increased (P＜0.05). Compared with miR-101 agomir group, the myocardial tissue lesions and fibrotic area in coumermycin A1 group significantly increased (P＜0.05), the level of LVESD, LVEDD, L-1β, IL-6, TNF-α, collagenⅠ, TGF-β, N-cadherin, vimentin, p-JAK2 and p-STAT3 was increased (P＜0.05). The level of miR-101, LVEF, LVFS and E-cadherin was decreased(P＜0.05). Conclusions miR-101 inhibits myocardial inflammatory lesions, myocardial fibrosis and epithelial-mesenchymal fransition(EMT) process after AMI with a mechanism targeting at JAK2/STAT3 signaling pathway, thus alleviates ventricular remodeling in rats after AMI.

Key words: miR-101, JAK2/STAT3 signaling pathway, acute myocardial infarction, ventricular remodeling, myocardial fibrosis

中图分类号:

R542.2+2

武波, 郭昊, 钟曌, 刘军芳, 王琦, 郭继勃. 过表达miR-101抑制JAK2/STAT3信号通路减缓急性心肌梗死模型大鼠心室重构[J]. 基础医学与临床, 2025, 45(3): 281-289.

WU Bo, GUO Hao, ZHONG Zhao, LIU Junfang, WANG Qi, GUO Jibo. Over-expression of miR-101 alleviates ventricular remodelingin rat models with acute myocardial infarction by inhibiting JAK2/STAT3 signaling[J]. Basic & Clinical Medicine, 2025, 45(3): 281-289.

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