FoxO1变化对糖尿病小鼠心肌缺血/再灌注损伤的影响  

Effect of myocardial FoxO1 variation on cardiac ischemia/reperfusion injury in diabetic mice

作　　者：冯世栋[1] 孙璐[1] 路晓艳[1] 杨强[1] 刘静祎[1] 王海昌[1] 陶凌[1] 

机构地区：[1]第四军医大学西京医院心血管内科,陕西西安710032

出　　处：《心脏杂志》2012年第3期303-307,共5页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(81100136)

摘　　要：目的:观察心肌中插头转录因子O1(FoxO1)在糖尿病(DM)小鼠心肌中表达量变化及对小鼠心肌缺血/再灌注(I/R)损伤的影响。方法:将90只健康雄性Swiss小鼠随机分为5组:假手术(Sham)组、I/R组、DM+Sham组、DM+I/R组及DM+FoxO1SiRNA+I/R组,每组18只。采用高糖高脂饮食加链脲菌素(Streptozocin,STZ)腹腔注射诱导建立DM小鼠模型。采用FoxO1SiRNA心肌点注射下调心肌FoxO1表达。心肌I/R损伤模型的建立,采用结扎心脏冠状动脉左前降支30 min后再灌注方案实施。心肌再灌注3 h后,用原位缺口末端标法(TUNEL)检测心肌细胞凋亡。用ELISA法检测心肌中Caspase-3的活性。用Western blot法检测心肌中FoxO1的表达量。心肌再灌注24 h后,用2,3,5-三苯基氯化四氮唑(TTC)染色法检测心肌梗死(MI)的面积。结果:与Sham组比较,DM+Sham组心肌中FoxO1的表达量明显增高(P<0.01)。与I/R组比,DM+I/R组MI的面积增大(P<0.05),心肌细胞凋亡数量及Caspase-3活性明显增加(P<0.01)。与DM+I/R组相比,DM+FoxO1SiRNA+I/R组心肌FoxO1的表达量下调(P<0.05),MI面积及Caspase-3的活性减小(P<0.05),心肌细胞凋亡数量减少(P<0.01)。结论:DM小鼠心肌中FoxO1表达量的增加可加重心肌I/R损伤;而下调心肌中FoxO1的表达量后,心肌I/R损伤减轻。To investigate the effect of myocardial FoxO1 expression on myocardial ischemia/reper- fusion injury in diabetic mice. METHODS： Ninety male Swiss mice were randomly divided into five groups： control group, I/R group, DM ＋ control group, DM ＋ I/R group, and DM ＋ FoxO1SiRNA ＋ I/R group. Diabetic mice model was induced by low-dose i.p. STZ injection along with a diet high in sugar and fat. The FoxO1SiRNA interference was implemented by injection into the apex and anterolateral wall of the heart. Myocardial isehemia injury was produced by slip-knot ligature of the left anterior descending coronary artery for 30 rain, and the myocardium was reperfused for 3 h （ for FoxO1 expression by Western blot, caspase-3 by ELISA and apoptosis by TUNEL） or 24 h （for infarct size by Trc staining）.

关 键 词：插头转录因子O1 糖尿病 缺血/再灌注损伤 心肌 

分 类 号：R587.1[医药卫生—内分泌]