MicroRNA-451对大鼠心肌缺血/再灌注损伤的影响  

Effects of MicroRNA-451 on Myocardial Ischemia/Reperfusion Injury in Rats

作　　者：胡笑容[1] 谢菁[1] 胡钢英[1] 周晓亚[1] 马瑞松 江洪[1] 

机构地区：[1]武汉大学人民医院心内科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2016年第6期866-870,874,共6页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:81100146;81370308)

摘　　要：目的:探讨MicroRNA(miR)-451在大鼠心肌缺血/再灌注(I/R)损伤中的作用及其作用机制。方法:将70只SD大鼠随机分为5组:假手术组(SO)、缺血再灌注组(I/R)、腺病毒空载体组(I/R+Ad-GFP)、miR-451上调组(I/R+Ad-miR-451)、miR-451下调组(I/R+Ad-asmiR-451)。心肌注射病毒液(1×1010 pfu/只)或PBS液(150μl/只)后3d建立缺血30min再灌注24h的心肌I/R模型。应用TTC+伊文思蓝双染法测定各组心肌梗死面积百分比,TUNEL法检测凋亡率,Western Blot法测定HMGB1和Caspase 3活化片段含量,应用试剂盒检测血清CK、LDH含量以及心肌组织SOD、MDA含量。结果:再灌注24h后,与SO组相比,I/R组和I/R+Ad-GFP组血清CK、LDH含量明显升高,心肌组织SOD活性降低、MDA含量升高,心肌组织HMGB1及Caspase-3活化片段蛋白含量显著上升,心肌细胞凋亡指数明显增加(以上P<0.05);与I/R组、I/R+Ad-GFP组相比,I/R+Ad-miR-451组血清CK、LDH含量显著下降,心肌组织SOD活性上升、MDA含量下降,心肌组织HMGB1和Caspase-3活化片段蛋白含量下降,心肌梗死面积百分比降低,心肌细胞凋亡指数降低(以上P<0.05);与I/R组、I/R+Ad-GFP组相比,I/R+Ad-asmiR-451组血清CK、LDH含量无明显上升,心肌组织MDA含量及SOD活性无明显变化,心肌组织HMGB1表达含量无明显上升,心肌梗死面积百分比及心肌细胞凋亡指数无显著升高(以上P>0.05),Caspase-3活化片段蛋白含量上升(P<0.05)。结论:MicroRNA-451通过调控HMGB1的表达,减轻凋亡和氧化应激进而减轻心肌I/R损伤。Objective：To investigate the effects of miR-451 on myocardial ischemia/reperfusion（I/R）injury in rats.Methods：Seventy male Sprague-Dawley rats were randomly divided into 5groups：Sham-operation（SO）group,I/R group,I/R＋Ad-GEP group,I/R＋Ad-miR-451,and I/R＋AdasmiR-451 group.At 24 hafter reperfusion,the concentrations of LDH and CK in serums were measured;the MDA concentration and SOD activity in tissues were examined;the infarct area was defined by TTC and Evans＇Blue;apoptoses in heart sections were measured by TUNEL staining;and the expressions of HMGB1 and cleaved-Caspase 3were detected by Western Blotting.Results：After 24hours＇reperfusion,the upregulation of miR-451 could significantly reduce the infarct size and the apoptosis of cardiomyocytes and the levels of LDH and CK（all P〈0.05）,compared with those in the I/R group and I/R＋Ad-GFP group;Meanwhile,the up-regulation of miR-451 could also significantly inhibit the expression of HMGB1,the increase of the MDA level and the decrease of the SOD level（all P〈0.05）.However,compared with those in the I/R group and I/R＋Ad-GFP group,the results of downregulation of Ad-miR-451 did not change statistically except for cleaved-caspase 3.Conclusion：The present study suggests that the up-regulation of miR-451 can allenuate myocardial I/R injury by inhibiting HMGB1 expression.

关 键 词：microRNA-451 心肌缺血 再灌注 高迁移率族蛋白1 

分 类 号：R541.4[医药卫生—心血管疾病]