辛伐他汀对急性心肌梗死大鼠血红素加氧酶-1的影响

目的探讨大鼠急性心肌梗死后心肌内血红素加氧酶-1(HO-1)水平变化及辛伐他汀对HO-1表达的影响。方法结扎♂SD大鼠冠状动脉左前降支建立心肌梗死模型,24 h后存活大鼠随机分为心肌梗死组(MI组)、辛伐他汀(Sim组)和假手术组(Sham组,只穿线不结扎)。Sim组以辛伐他汀40 mg.kg-1.d-1灌胃,MI组和Sham组以等体积生理盐水灌胃。术后24 h、7 d、28 d处死动物,RT-PCR及Western bolt测定心肌非梗死区HO-1 mRNA和蛋白表达水平,并测非梗死区心肌超氧化物岐化酶(SOD)活性、丙二醛(MDA)含量。结果HO-1 mRNA和蛋白表达水平均在心梗后24 h开始升高,7 d达峰,28 d恢复至基线水平。3个时间点MI组上述指标均高于Sham组;术后7 d和28 d Sim组上述指标均高于MI组(P<0.05)。随HO-1 mRNA和蛋白表达水平升高,SOD活性升高,MDA含量降低。结论心肌内HO-1水平在急性心肌梗死后28 d内呈现动态变化。辛伐他汀可诱导HO-1表达,发挥抗氧化损伤的心脏保护作用。

Effects of simvastatin on heme oxygenase-1 in acute myocardial infarction rats

Aim To investigate the changes of heme oxygenase-1(HO-1) in cardiomyocytes after acute myocardial infarction and the impact of simvastatin on HO-1 expression in rats.Methods Myocardial infarction models were made by anterior descending coronary artery ligation on male SD rats whereas sham group by spurious ligation.Survivals were randomized into myocardial infarction(MI) group,simvastatin(Sim) group and sham group 24 hours after the operation.The Sim group was treated with simvastatin 40 mg·kg-1·d-1 via gavage till sacrifice.MI and sham groups were gavaged with equal volume of 0.9% NaCl at the same time.Rats were sacrificed at time points of 24 hours,7 days and 28 days after the operation,for the detection of HO-1 mRNA by RT-PCR,HO-1 protein level by Western bolt,activity of superoxide dismutase(SOD) and content of malondialdehyde(MDA) by spectrophotometric method in non-infarcted zone.Results Expression of HO-1 mRNA and protein level increased at 24 hours,peaked at 7 days and decreased to basal levels at 28 days.All the indexes at each time point mentioned above were significantly higher in MI group than those in sham group.At the 7th day and 28 th day after the operation,the indexes were higher in Sim group than those in MI group(P<0.05).The increase of HO-1 mRNA and protein expression were accompanied by increased activity of SOD and decreased content of MDA in different groups of treatment at each time point.Conclusion The expression of HO-1 changes dynamically within 28 days after acute myocardial infarction.One of the possible mechanisms of simvastatins antioxidative cardiol protection may be through the induction of HO-1.