Effect Of Simvastatin On FOXO3A Expression And Ventricular Remolding In Post-Myocardial Infarction Rats

Objective: To assess the effect of simvastatin on ventricular remodeling in post-myocardial Infarction RatsMethod: Twenty-four hours after myocardial infarction by left anterior descending coronary artery ligation, the survival rats were randomly divided into myocardial infarction group (MI, n = 8) , simvastatin 20 mg/kg·d treatment group (Sim,n =8). Sham-operated animals underwent identical surgery except for the coronary artery ligation (Sham, n =10). After 4 weeks, the effects of sinvastatin on myocardial fibrosis were evaluated by detecting changes of left ventricular mass index (LVMI), the collagen volume fraction (CVF) in non-infarction zone (NIZ) with Picric-Sirius Red Polarimetry, the myocardial histopathology was also examined by HE staining. The datas were analysed by SAS 9.1software. Result :(1)Comparing with Sham group, the LVMI was increased significantly in MI group. In comparison with MI group, the LVMI was decreased significantly in Sim group (P<0.05), but still higher than those in Sham group(P<0.05).(2)Compared with Sham group, the type I CVF, the type III CVF in NIZ and the I/III ratio were increased significantly in MI and Sim groups(P<0.05).To Compare with MI group, the type I CVF, the type III CVF in NIZ and the I/III ratio were was decreased significantly in Sim groups(P<0.05).(3)The result of HE staining showed that the cardiomyocytes in Sham-operated rats arranged regularly in good strike without disturbance of myofilament and the intercellular space of the cardiomyocytes were uniform with infiltration of a few inflammatory cells; The MI group showed significantly reduced cardiomyocytes that were substituted by numerous strip-like fasciculation collagen fiber and structurally disordered; and in the non-infarcted region of MI rats, infiltration of considerable inflammatory granulocytes and monocytes and proliferation of protofibrocytes, and compensatory hypertrophy of the survival cardiomyocytes were noted. Compared to MI group, Simvastatin-treated groups showed significantly improved in the non-infarcted region. Conclusion: All post-myocardial Infarction Rats showed ventricular remodeling.Simvastatin has a protective effect on myocardial injury and can ameliorate ventricular remodeling in rats induced by MI.Part I I Effect of Simvastatin on Fox03a Expression in Post-myocardial Infarction RatsObjective: To investigate the effect of simvastatin on FoxO3a in ventricular remodeling Post-myocardial Infarction RatsMethod: Twenty-four hours after myocardial infarction by left anterior descending coronary artery ligation, the survival rats were randomly divided into myocardial infarction group (MI, n = 8) , simvastatin 20 mg/kg·d treatment group (Sam, n=8). Sham-operated animals underwent identical surgery except for the coronary artery ligation (Sham, n=10). After 4 weeks, the expressions of FoxO3a in NIZ by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry staining and Western-blot. The datas were analysed by SAS 9.1 software.Result:(1)RT-PCR: Comparing with Sham group, the expressions of FoxO3a mRNA in NIZ were decreased significantly in MI and Sam groups (P<0.05); To compare with MI group, the expressions of FoxO3a mRNA were significantly increased in Sim groups (P<0.05).(2)Immunohistochemistry staining: FoxO3a protein mainly expressed in the nucleus of myocardial cells. Compared with Sham group, the expressions of FoxO3a in protein level by immunohistochemistry were significantly decreased in MI group(P<0.05); comparing with MI group, the expressions of FoxO3a protein were significantly increased in Sim groups(P<0.05),but higher than those in Sham group(P<0.05).(3)Western-blot:As compared with Sham group, the expressions of FoxO3a in protein level by Western-blot were significantly decreased in MI and Sim groups(P<0.05); comparing with MI group, the expressions of FoxO3a protein were significantly increased in Sim groups(P<0.05).Conclusion: The expressions of FoxO3a in NIZ of left ventricular in MI rats were down-regulated. The mechanisms of simvastatin anti-ventricular remodeling could be associated with its effects of up-regulating FoxO3a.