洛伐他汀预适应在大鼠急性心脏缺血再灌注损伤中的心肌保护作用研究

Myocardial protective effect of Lovastatin preconditioning during ischemia-reperfusion injury in rats

目的探讨洛伐他汀(Lovastatin)预适应在大鼠急性心脏缺血再灌注损伤中的心肌保护作用机制。方法将24只Sprague-Dawley(SD)大鼠随机分洛伐他汀组(A组),每天胃内直接灌注洛伐他汀15mg/kg,灌注时间2周;洛伐他汀复合L-硝基精氨酸甲酯(L-NAME)(B组),每天胃内直接灌注洛伐他汀15mg/kg,同时每天腹腔内注射L-NAME30mg/kg,共2周;模型对照组(C组)。2周后建立在体急性缺血再灌注心脏模型,观察心肌组织内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)mRNA的表达以及心肌细胞的凋亡情况。结果洛伐他汀能明显上调缺血再灌注时心肌组织内eNOSmRNA表达(t=0.006,P<0.01);下调iNOSmRNA的表达(t=0.0002,P<0.01);明显降低缺血再灌注所导致的心肌细胞凋亡指数(t=0.03,P<0.05)。结论洛伐他汀预适应对大鼠心脏急性缺血再灌注时具有心肌保护作用,与其在缺血再灌注过程中eNOSmRNA表达提高及iNOSmRNA表达抑制有关。

Objective To investigate the myocardial protection effect of lovastatin preconditioning during ischemia-reperfusion injury in rats. Methods Twenty four Sprague-Dawiey male rats were randomly divided into three groups with 8 in each. In group A, 15mg/kg lovastatin was given orally once a day; in group B 15mg/kg lovastatin was given orally and 30mg/kg L-NAME was given intraperitoneally; in group C no preconditioning was given. Ischemic-reperfusion injury models of rat heart were established with coronary occlusion for 30 rain and reperfusion for 30 minutes of the left anterior descending artery two weeks after drug preconditioning. The expression of eNOS and iNOS mRNA and the myocardial apoptosis in the heart tissue were examined. Results Compared with group C, the eNOSmRNA expression was up-regulated （t=0.006, P〈0.01） and the iNOSmRNA expression was down-regulated （t=0.0002, P〈0.01） in group A. The index of apoptosis in the group A was also decreased （t=0.03, P〈0.05）. Conclusion Lovastatin preconditioning may protect myocardium from ischemia-reperfusion injury of rats, which might be associated with up-regulation of eNOS expression and down-regulation of iNOS expression.