miR-21调控gp130/JAK2对心肌梗死大鼠心室重构、JNK信号通路及心肌保护的作用  

The effects of miR-21 on the ventricular remodeling, NK signaling pathway and myocardial protection in rats with myocardial infarction by regulating gp130/JAK2

作　　者：冯月英 施惠华 戴蓉芳 FENG Yueying;SHI Huihua;DAI Rongfang(Department of Gerontology,The Ninth People’s Hospital Affiliated to Medical School of Shanghai Jiao Tong University,Shanghai 201999,China)

机构地区：[1]上海交通大学医学院附属第九人民医院老年科,上海市201999

出　　处：《河北医药》2022年第23期3538-3543,共6页Hebei Medical Journal

基　　金：上海市宝山区科学技术委员会科研项目计划(编号:10-E-1)。

摘　　要：目的 探讨miR-21通过调控gp130/JAK2对心肌梗死大鼠心室重构、JNK信号通路及心肌保护的作用。方法 将40只雄性大鼠随机分为sham组、MI组、NC组及实验组,除sham组其余大鼠均建立心肌梗死大鼠模型,NC组及实验组建模后分别冠状动脉注射miR-21-NC及miR-21-mimics病毒载体,sham组及MI组用大鼠心脏冠状动脉注射PBS缓冲液,采用RT-PCR检测各组大鼠心肌组织中miR-21表达;TCC方法检测各组大鼠心肌梗死面积;HE染色观察心肌组织病理形态;HPIAS2000型医学图象分析系统心肌组织胶原占比;TUNEL法检测心肌细胞凋亡率;免疫印迹及PCR分别检测各组大鼠心肌组织GP130、JAK2及JNK表达。建立心肌细胞缺氧模型,通过添加miR-21-NC及miR-21-mimics病毒载体共培养,观察miR-21对gp130/JAK2的调控作用。结果 与sham组比较,MI组大鼠心肌组织中miR-21mRNA表达降低(P<0.05),MI组及NC组差异无统计学意义(P>0.05),与NC组比较,实验组大鼠心肌组织中miR-21mRNA表达升高(P<0.05);sham组、MI组、NC组及实验组大鼠心肌梗死面积差异有统计学意义(P<0.05);与sham组比较,MI组非梗死区域的PVCA和CVF增加(P<0.05),MI组与NC组非梗死区域的PVCA和CVF差异无统计学意义(P>0.05),与NC组比较,实验组大鼠非梗死区域的PVCA和CVF降低(P<0.05);Sham组大鼠心肌细胞排列整齐,结构完整,无炎症浸润;MI组及NC组大鼠心肌细胞紊乱及数目减少,排列紊乱出现大量肌肉丝溶解及炎症浸润,与NC组比较,实验组大鼠心肌细胞紊乱有效改善,炎症浸润逐渐降低,sham组、MI组、NC组及实验组大鼠心肌细胞凋亡率差异有统计学意义(P<0.05);与sham组比较,MI组大鼠心肌组织GP130及JNK升高,JAK2降低(P<0.05),MI组与NC组心肌组织GP130、JNK、JAK2差异无统计学意义(P>0.05),与NC组比较,实验组大鼠心肌组织GP130及JNK降低,JAK2升高(P<0.05);抑制miR-21观察对GP130、JAK2的荧光活性变化,证实抑制miR-21能够抑制GP130活性,激Objective To investigate the effects of miR-21 on the ventricular remodeling, NK signaling pathway and myocardial protection in rats with myocardial infarction by regulating gp130/JAK2.Methods Forty male rats were randomly divided into sham operation group, MI group, NC group and experimental group.The rat models with Myocardial infarction were established in the rats except for those in sham operation group.After modeling, miR-21-NC and miR-21-mimics virus vectors were injected into the coronary arteries of rats in NC group and experimental group, respectively.The rats in sham operation group and MI group were injected with PBS buffer into the coronary arteries of rats, and the expression levels of miR-21in the myocardial tissues of rats were detected by RT-PCR.TCC method was used to detect the size of myocardial infarction;HE staining was used to observe the pathological morphology of myocardial tissue.Moreover the collagen ratio of myocardial tissue was analyzed by HPIAS2000 medical image analysis system;TUNEL assay was used to detect the apoptosis rate of myocardial cells;Western Blot and PCR were used to detect the expression levels of GP130,JAK2 and JNK in myocardial tissues.In addition the regulatory effects of miR-21 on gp130/JAK2 by adding miR-21-NC and miR-21-mimics virus vector co-cultivation were observed.Results Compared with those in sham operation group,the expression levels of miR-21mRNA in myocardial tissue of rats in MI group were significantly decreased(P<0.05),however, there were no significant differences between MI group and NC group(P>0.05).Compared with those in NC group, the expression levels of miR-21mRNA in experimental group were significantly increased(P<0.05).Moreover there were significant differences in the myocardial infarction areas among sham operation group, MI group, NC group and experimental group(P<0.05).Compared with those in sham operation group, the levels of PVCA and CVF in the non-infarct area in MI group were significantly increased(P<0.05),however, there were no signi

关 键 词：心肌梗死 MIR-21 心室重构 GP130 Janus酪氨酸激酶 

分 类 号：R542.22[医药卫生—心血管疾病]