Effect of simvastatin on ventricular remodeling in rats after myocardial infarction

Objective To study the effect of simvastatin on improve ventricular remodeling in rats after myocardial infarction(MI). Methods The MI models of rat were constructed,and divided into three groups:(1)MI group(MI-C),only ligation of left anterior descending coronary artery(LAD);(2)Simvastatin group(MI-S),ligation of LAD and gavage with simvastatin 40 mg·kg~(-1)·d~(-1);(3)Sham group(sham),no ligation of LAD.Cardiac architecture and function were determined by the echocardiography.The TNF-α mRNA expression in infarction and non-infarction regions was measured by RT-PCR. TNF-α protein was determined by Western blot and immunohistochemical staining.Results The echocardiography showed that the left ventricular end-diastolic diameter(LVEDd,(7.5±0.4)mm versus(4.5±0.3)mm) significantly increased in MI-C group,compared with sham group.The fractional shortening(FS,(20.5±2.5)% versus(51.6±3.1)%) and ejection fraction(EF,(41.4±4.3)%versus(85.2±3.7)%)markedly decreased in MI-C group,while compared with sham group. Simvastatin obviously reduced left ventricle(LV) expansion and improved LV function(P0.05).The mRNA expression and protein production of TNF-α markedly increased in MI-C group compared with sham group(P0.01),and mRNA expression and protein production of TNF-α markedly lowered in MI-S group compared with MI-C group(P0.01).The protein of(TNF-α) mainly located in live myocardial cells of non-infarction and infarction regions,and simvastatin significantly decreased protein production of TNF-α.There existed a positive correlation between mRNA expression of TNF-α and depressed cardiac function.Simvastatin decreased mRNA expression of TNF-α and improved cardiac function. Conclusions Simvastatin may improve ventricular remodeling in rats after MI.The mechanism maybe related to simvastatin-decreasled gene expressionand protein production of TNF-α in non-infarction and infraction region.