洛伐他汀预适应在大鼠急性缺血再灌注中的心肌保护作用

The study of myocardial protection and its mechanisms of lovastatin preconditioning in the ischemic and reperfused rat hearts

目的:探讨洛伐他汀预适应对大鼠心脏急性缺血再灌注中的心肌保护作用及其机制。方法:将 24只SD大鼠随机分为3组(每组均8只):模型对照组(C组); 洛伐他汀组( L组),胃管直接灌注洛伐他汀 15 mg·kg-1·d-12周;洛伐他汀复合L 硝基精氨酸甲酯(L NAME)组(N组),洛伐他汀直接灌胃 2 周同时腹腔注射L NAME 30 mg·kg-1·d-1;2周后建立体内急性缺血再灌注心脏模型,监测缺血再灌注前后血流动力学各项指标,同时观察各组血脂水平及其血浆中丙二醛(MDA) 、心肌组织内超氧化物歧化酶(SOD)变化情况。结果: L组和N组较C组心率明显变慢(P<0.01),缺血再灌注心律失常消失和再灌注时-dp/dtmax下降明显改善(P<0.05);同时各项血脂指标不变,洛伐他汀能明显减少再灌注时血浆中MDA生成, 并且提高心肌组织SOD活性(P<0.05)。结论:洛伐他汀预适应对体内大鼠心脏急性缺血再灌注时具有非降脂外的心肌保护作用,其机制除与其增加一氧化氮(NO)合成相关外,可能还有其他物质或途径参与。

Objective:To investigate the protective effect of lovastatin on the ischemic and reperfused rat myocardium and its mechanism. Method:Twenty-four Sprague-Dawley male rats were randomly and evenly divided into three groups: model control group; Lovastatin group treated with 15 mg lovastatin per a kilogram once a day; L-NAME group treated with the same dose of lovastatin with lovastatin group and L-NAME 30 mg per a kilogram once a day. Rat models of I/R were established with coronary occlusion 30 mintues and reperfusion 30 mintues of the left anterior descending artery after two-week's administration. Hemodynamics was monitored during the period of ischemia and reperfusion. Superoside dismutase of myocardial tissue and malondialdehyde in blood serum were measured as well as lipin in blood serum. Result: In comparison with model control group, heart rate was reduced markedly and reperfused arrhythmia disappeared in the L group and N group.The descent of -dp/dt in the reperfused period was improved in both L and N group. Without lipin in the blood serum changed, Lovastatin decreased the yield of malondialdehyde(MDA) in the blood serum and rise the activity of superoside dismutase (SOD)in the myocardial tissue after ischemia and reperfusion.Conclusion: Lovastatin may have the protective effect on the ischemic and reperfused rat myocardium,but such effects didn't correclate to its effect on lipin in blood serum.There may have another something or pathway which correclate to its effect as well as NO synthesis increasing.