Proteasome inhibitor MG-132 improves left ventricular remodeling after myocardial infarction in rats

Objective To investigate the effects and possible mechanisms of proteasome inhibitor MG-132 on left ventricular remodeling following acute myocardial infarction in rats.Methods The myocardial infarction model in rats was induced by ligating left anterior descending coronary artery.Thirty-two adult Sprague-Dawley rats that survived 24 h after acute myocardial infarction were randomly divided into myocardial infarction(MI) group and MG-132-treated(MG) group.Sixteen matchable rats were designated as sham-operated group(SH group).Rats in MG group were treated with MG-132(0.1 mg/kg,i.p.daily) for 28 d,while rats in MI group and SH group were given normal saline as control.On 28th day,the changes of left ventricle structure were measured by echocardiography.The left weight index and infarct size were evaluated.The mRNA and protein levels of NF-κB p65 and IL-1β were determined by reverse transcription-polymerase chain reaction(RT-PCR) and by Western blot,respectively.Results Compared with SH group,the values of left ventricle posterior wall thickness(LVPWT) and left ventricle end diastolic diameter(LVEDD) were significantly increased in MI group and MG group(P0.01).However,the values of left ventricle anterior wall thickness(LVAWT) were remarkably decreased(P0.01).The values of LVPWT,LVEDD and LVW/BW in MG group were notably decreased than those in MI group(P0.01),whereas the changes of LVAWT in MG group increased(P0.01).Moreover,the mRNA and protein levels of NF-κB p65 and IL-1β in MG group were lower than those in MI group(P0.01).Conclusion Left ventricular remodeling following acute myocardial infarction could be improved by proteasome inhibitor MG-132 through suppressing NF-κB activation and the expression of inflammatory factor such as IL-1β in rats.