蛋白酶体抑制剂MG-132改善大鼠心肌梗死后心肌肥厚

摘要

目的 探讨蛋白酶体抑制剂MG-132对大鼠心肌梗死后心肌细胞肥大的影响及机制.方法 制作大鼠心肌梗死模型,随机分为MG-132干预(MG)组和心肌梗死(MI)组,另设假手术(sham)组,每组6只.MG组于术后24 h腹腔注射MG-132[0.1 mg/(kg·d)],MI组及SH组注射0.9％氯化钠注射液对照.连续给药28 d后超声检测心脏左室后壁厚度；称取左室重量,计算左室质量指数；计算非梗死区心肌细胞面积、周长及平均直径.RT-PCR和免疫组化分别检测核转录因子-κB P65 (NF-κB P65)及白介素-1β(IL-1β)的mRNA和蛋白质表达量.结果 与SH组比较,MI组和MG组的左室后壁厚度、左室质量指数、心肌细胞的直径、周长和表面积明显增大,NF-κB P65和IL-1β的mRNA及蛋白质表达量明显增加(P＜0.01).MG组的上述指标明显低于MI组(P＜0.01).结论 MG-132在一定程度上能改善大鼠心梗后心肌细胞肥大,其机制可能与抑制NF-κB激活,下调炎性细胞因子如IL-1β表达有关.%Objective To investigate the effects and possible mechanisms of Proteasome inhibitor MG-132 on myocadial hypertrophy following acute myocardial infarction in rats. Methods The myocardial infarction model in rats was induced by ligation of left anterior descending coronary artery. 12 adult sprague-dawley rats that survived 24 hours after acute myocardial infarction were randomly divided into myocardial infarction (MI) group and MG-132-treated(MG) group. Six were designated as sham-operated group(SH)group. Rats in MG group were treated with MG-132(0. 1 mg/kg, daily)through intraperitoneal injection for 28 days, rats in MI group and SH group were given normal saline as control. On 28th day, left ventricle posterior wall thickness was measured by echocardiography and the left weight index was evaluated. The myocardial cell direct, perimeter and surface area in non-infarct area were quantified histomorphometry. The mRNA and protein levels of NF-kappaB P65 and IL-1β were determined by reverse transcription - polymerase chain reaction (RT-PCR) and by immunohistochemistry, respectively. Results　Compared with SH group, the values of left ventricle posterior wall thickness and the left weight index were significantly increased in MI group and MG group(P <0.01). The values of myocardial cell direct, perimeter and surface area in non-infarct area were significantly increased in MI group and MG group(P <0. 01). However, the values of above makers in MG group were notably decreased as compared with those in MI group(P <0. 01 ). Moreover,the mRNA and protein levels of NF-kappaB P65 and IL-1 βin MG group were lower than those in MI group (P < 0. 01) . Conclusions Myocadial hypertrophy following acute myocardial infarction is improved by MG-132 through suppressing NF-kappaB activation and the expression of inflammatory factor such as IL-1β in rats.