FoxO1变化对糖尿病小鼠心肌缺血/再灌注损伤的影响

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。

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

AIM: To investigate the effect of myocardial FoxO1 expression on myocardial ischemia/reperfusion 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 ischemia injury was produced by slip-knot ligature of the left anterior descending coronary artery for 30 min,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 TTC staining).RESULTS: Compared with the control group,FoxO1 expression of myocardium increased in DM+control group(P<0.01).Compared with I/R group,the infarct area size(P<0.05),myocardial apoptosis and caspase-3 activity(P<0.01) increased in DM+I/R group.After decreasing myocardial FoxO1 expression in DM+FoxO1SiRNA+I/R mice(P<0.05),caspase-3 activity(P<0.01),infarct area size and myocardial apoptosis(P<0.05) decreased in DM+FoxO1SiRNA+I/R group compared with DM+I/R group.CONCLUSION: High expression of myocardial FoxO1 increases cardiac vulnerability to myocardial I/R injury in diabetic mice.Downregulation of myocardial FoxO1 expression attenuates myocardial I/R injury.