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.