Interference with TLR4 Signal Pathway and Attenuatiou of Ventricular Remodeling by Simvastatin in Rat with Myocardial Infarction

Objective To study the effect of simvastatin on TLR4,TNF-α and IL-6 expression in myocardium and its relation to ventricular remodeling in rat with myocardial infarction(MI).Methods The MI models of rat were established by ligation of left anterior descending(LAD) branch of coronary artery and randomized to the following groups: untreated MI;Simvastatin treatment [40 mg/(kg·d)] for 4 weeks;Sham group cardiac geometry and function were determined by the echocardiography.Expression of TLR4 mRNA and protein in myocardium in each group were measured by RT-PCR and Western blot;level of TNF-α and IL-6 in myocardial homogenate were measured by ELISA.Results LVEDd was significantly increased and ejection fraction(EF) and fractional shortening(FS) markedly decreased in MI rats;simvastatin obviously inhibited left ventricular dilation and improved left ventricular function after MI.Expression of TLR4 mRNA and protein,TNF-α and IL-6 in myocardium were significantly increased in MI group.Simvastatin markedly inhibited expression of TLR4 mRNA and protein,TNF-α and IL-6 in myocardium after MI.TLR4 protein was positively related to LVEDd,TNF-α and IL-6 respectively.Conclusion Simvastatin aneliorated ventricular remodeling after MI in rat which was associated with its inhibition of TLR4,TNF-α and IL-6 in myocardium expression.