洛伐他汀预处理的延迟性心肌保护作用及其机制

目的探究洛伐他汀在大鼠心脏急性缺血/再灌注中的延迟性心肌保护作用及其机制。方法SD大鼠24只随机分为3组（每组8只）:模型对照组（C）;Lovastatin组（L）,洛伐他汀直接灌胃两周15mg/（kg·d）;Lovastatin复合LNAME组（N）,洛伐他汀15mg/（kg·d）直接灌胃2周同时腹腔注射LNAME30mg/（kg·d）;2周后建立在体急性缺血/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MDA、SOD、LDH以及CK的变化情况。结果L组和N组较C组心率显著减慢（P<0.01）,缺血/再灌注心律失常消失和再灌注时-dp/dtmax下降显著改善（P<0.05）;各项血脂指标不变的情况下,洛伐他汀显著减少再灌注时血浆中MDA生成和LDH及CK的释放（P<0.01）,并且提高心肌组织SOD活性（P<0.05）。结论Lovastatin对在体大鼠心脏急性缺血/再灌注时具有非降脂外的延迟性心肌保护作用。NO合酶途径是其心脏保护作用的诸多途径之一。

Delayed myocardial protection and its mechanisms of Lovastatin preconditioning in the ischemic and reperfused rat hearts

AIM To investigate the delayed protective effects of Lovastatin on ischemic and reperfused (I/R) rat myocardium and its underlying mechanism. METHODS Twenty-four Sprague-Dawley male rats were randomly divided into three groups: the model control group, L group treated with Lovastatin (15 mg/kg per day), and N group receiving combination of Lovastatin (15 mg/kg per day) and L-NAME (30 mg/kg per day). Two weeks after the preconditioning, I/R model was set up in all rats via 30 min coronary occlusion followed by 30 min reperfusion of the left anterior descending artery. Hemodynamic measurement and measurement of superoxide dismutase (SOD), malondialdehyde (MDA), LDH and CK were done. RESULTS In both L and N group, heart rate reduced obviously, arrhythmia caused by reperfusion was not observed and the descent of dp/dt_ max was improved. Pre-treatment with Lovastatin decreased the yield of MDA, LDH and CK in the serum and enhanced the activity of SOD during I/R, while the level of blood lipid was found unchanged. CONCLUSION Lovastatin may have a delayed protective effect on I/R myocardium not through reduction of blood lipid.