The Effect Of Atorvastatin On Cardiac Function In Myocardial Hypertrophy And Heart Failure Rats And The Possible Mechanisms

Objective:To study the effect of atorvastatin on cardiac function, Adiponectin(APN),matrix metalloproteinases-9(MMP-9),tissue inhibitors of metalloproteinases-1(TIMP-1),left ventricular weight index in myocardial hypertrophy and heart failure rats, and investigate the possible mechanisms.Methods:Myocardial hypertrophy model was induced by isoprenaline and heart failure model was induced by doxorubicin.In each model,30 SD rats were selected and randomly divided into untreated group(15 rats) and atorvastartin treated group(15 rats).Another normal 20 SD rats were served as the control group.In atorvastatin treatment, 20mg/kg/d were fed stomachically. Equivalent distilled water was used in the control group.After 4 weeks'treatment, the rats were killed; the body weight and the left ventricular weight were measured; the left ventricular weight index(left ventricular weight/body weight) were calculated;the left ventricular end-diastolic diameter(LVEDD),the left ventricular end-systolic diameter(LVESD), the left ventricular ejection fraction(LVEF), the end-diastolic interventricular septum thickness(IVS), and the left ventricular Fraction shortening(LVFS) were measured through echocardiographic.The serum level of APN was measured by ELISA. Myocadiocyte MMP-9 and TIMP-1 were analyzed by Immunohistochemistry.Results:(1)In the myocardial hypertrophy group,the IVS level,the left ventricular weight index and the positive rate of MMP-9 were significantly increased (p<0.05) compared to that in the control group, while the APN concentration and the positive rate of TIMP-1 were significantly decreased (p<0.05).A negative correlation was found between MMP-9 and TIMP-1.In the heart failure group, LVEDD, LVESD, APN, and the positive rate of MMP-9 were significantly increased (p<0.05) compared to that in the control group,while LVEF, the body weight, the left ventricular weight, and the positive rate of TIMP-1 were significantly decreased (p<0.05).A negative correlation was found between APN and LVEF, TIMP-1 and LVEF, MMP-9 and TIMP-1;a positive correlation between MMP-9 and LVEF.(2)After treatment with atorvastatin in the myocardial hypertrophy group,the IVS level,and the positive rate of MMP-9 were significantly decreased (p<0.05),while the APN concentration and the positive rate of TIMP-1 were significantly increased (p<0.05).After treatment with atorvastatin in the heart failure group,the APN concentration and the positive rate of MMP-9 were significantly decreased and the positive rate of TIMP-1 was significantly increased (p<0.05).No significant changes were observed in LVEDD, LVESD, LVEF,FS (p>0.05).Conclusion:(1)Isoprenaline induced myocardial hypertrophy in SD rats,with MMP-9 increased and APN and TIMP-1 decreased. Doxorubicin induced heart failure with MMP-9 and APN increased and TIMP-1 decreased.(2) Treatment with atorvastatin, cardiac function was improved; TIMP-1,APN increased and MMP-9 decreased in myocardial hypertrophy rats;MMP-9,APN decreased and TIMP-1 increased in heart faiure rats.(3)Atorvastatin can adjust the expression of APN, MMP-9 and TIMP-1,which might partly explain its role in improving cardiac function.