负荷剂量氟伐他汀对心肌缺血再灌注损伤的保护作用——模拟缺血预适应

Research on the effect of loading dose fluvastatin preconditioning on myocardial reperfusion injury in rats

目的观察负荷剂量氟伐他汀预处理对在体大鼠心肌缺血再灌注损伤的保护作用。方法 84只大鼠随机分为12组,每组7只。其中氟伐他汀组（F-1~F-8组）分别于冠状动脉缺血前1、2、4、6、12、24、48和72 h灌胃氟伐他汀80 mg/kg;假手术组（Sham组）、缺血再灌注组（I/R组）、缺血预适应第一窗口组（IPC-1组）及第二窗口组（IPC-2组）灌胃等量生理盐水。建立大鼠心肌缺血再灌注损伤模型、缺血预适应保护模型及延迟保护模型。记录大鼠心律失常及心肌缺血、心肌梗死情况,测定血清乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）活性,光学显微镜及透射电镜下观察受损心肌细胞形态。结果氟伐他汀预处理组中,除F-5、F-6组外,其他组心肌梗死面积均较I/R组减小（P〈0.05）;负荷剂量氟伐他汀的保护作用呈现两个窗口,F-3、F-7组分别为其保护作用的最佳组（与I/R组比较,P〈0.05）;与IPC-1组比较,F-3组心肌缺血、心肌梗死程度、血清LDH和CK-MB均显著增高（P〈0.05）,心律失常评分差异无统计学意义（P〉0.05）。与IPC-2组比较,F-7组梗死面积有减少趋势（P〉0.05）,心肌梗死质量显著降低（P〈0.05）,缺血程度显著增高（P〈0.05）。结论负荷量氟伐他汀预处理对在体大鼠心肌缺血再灌注损伤的保护作用存在两个窗口,第一窗口较缺血预适应弱,第二窗口在减轻心肌梗死程度上有强于缺血预适应的趋势。

Objective To investigate the effect of a single loading dose fluvastatin pretreatment on myocardial reperfusion injury,and then compare it with ischemic preconditioning（ IPC）. Methods 84 SD rats were randomly divided into 12 groups（ n = 7 in each group）. In the F-1-F-8（ fluvastatin preconditioning） group,the animals were treated with loading dose fluvastatin（ 80 mg / kg） 1 h,2 h,4 h,6 h,12 h,24 h,48 h or 72 h before the myocardial ischemia. In the sham group,I / R（ ischemic /reperfusion） group and IPC（ ischemic preconditioning） group,the animals were treated with the same amount of saline orally. The model of I / R,IPC and delayed-IPC were established. The arrhythmia scores（ AS） were recorded. Plasma CK-MB activity,LDH activity and myocardial ischemia/infracted range were measured. The myocardial ultrastructure was observed by optical microscopy and transmission electron microscope. Results For the myocardial infracted area ratio of fluvastatin preconditioning groups,there was no signifi cant difference among F-5,F-6 and I / R group（ P 〉 0. 05）. Two protection windows were shown with F-3 and F-7 group were the ones with the best protection separately when compared with the I / R group（ both P 〈 0. 05）. Compared with the IPC-1 group,the degree of myocardial injury,plasma CK-MB and LDH activity of F-3 were signifi cantly increased（ P 〈 0. 05）,but not include AS（ P 〉 0. 05）. Compared with the IPC-2 group,the F-7 group showed a signifi cantly decrease in the myocardial infracted weight ratio（ P 〈 0. 05）,a decreasing trend in the myocardial infracted area ratio（ P 〉 0. 05）,but a increasing trend in the myocardial ischemia weight ratio（ P 〈 0. 05）. Conclusions The time course of loading dose of fluvastatin preconditioning shows double windows of protection to myocardial IRI. The early phase protective effect of loading dose of fluvastatin preconditioning to myocardial IRI is less potent than IPC,but the late phase act similar,and even stronger in decreasing the degree of myocardial infarction.