Effect of Simvastatin on GSK3β Activity and the Protein Expression of GSK3β and β-Catenin in Chronic Heart Failure Rabbit Models

Objective:To observe the effect of simvastatin on myocardial remodeling and cardiac function in chronic heart failure(CHF)rabbit models,and to explore the underlying mechanism by analyzing GSK3β and β-catenin.Methods:Twenty-four New Zealand rabbits were divided into four groups and each group contained six animals.Group①:Healthy control group,the rabbits received sham operation.In rest three groups,CHF rabbit model was created by coarctation of ascending aorta and aortic regurgitation.Group②:CHF control group,CHF rabbit received no medication.Group③:Early simvastatin treatment group,CHF rabbits were given simvastatin(5 mg/d·kg)after the operation for 8 weeks.Group④:Late simvastatin treatment group,CHF rabbits were given simvastatin(5 mg/d·kg) 4 weeks after the operation for 4 weeks.At the end of experiment,left ventricular end diastolic pressure(LVEDP)was measured with the catheter.Results:At 8 weeks of the operation,compared with the Healthy control group,the heart weight,left ventricular weight,heart/body weight radio,and left ventricular/body weight radio were significantly higher in CHF control group(all P0.01).Compared with CHF control group,the heart weight,left ventricular weight,heart/body weight radio were significantly lower in both Early and Late simvastatin treatment groups(P0.05~0.01).The LVEDP in Early and Late simvastatin treatment groups were significantly lower than that in CHF control group(P0.05).We found that the GSK3β activity significantly decreased and the expression of nuclear β-catenin significantly increased in CHF myocardium compared with healthy control(P0.01).Simvastatin significantly increased the GSK3β activity and inhibited the nuclear β-catenin expression in both Early and Late simvastatin treatment groups(P0.01).There were no significant differences of GSK3β protein expression among four groups.Conclusion:Simvastatin prevented the cardiac remodeling in CHF rabbit models and improved the cardiac function.The underlying mechanism might be related to the elevation of the GSK3β activity and the inhibition of nuclear β-catenin expression.