【摘要】 目的:探讨氟伐他汀对高脂血症兔心肌缺血再灌注损伤的保护作用及机制。方法:自制脂肪乳剂灌胃建立兔高脂血症模型。将40只高脂血症日本大耳白兔随机分为4组(每组10只):单纯缺血再灌注组(IR 组)、假手术组(S组)、氟伐他汀10 mg/kg剂量组(F10组)和75 mg/kg剂量组(F75组),实验中监测各组大兔心电图及心功能,实验毕取心肌组织,Evans蓝及氯化三苯基四氮唑(TTC)双重染色测心肌梗死程度,比色法测心肌一氧化氮合酶(NOS)同工酶活力。结果:缺血再灌注后,与IR组相比,F10组和F75组诱导型NOS(iNOS)活力显著降低(均P<0.01),心肌梗死程度显著降低(P<0.01),心功能显著改善。F75组与F10组相比,iNOS活力显著降低(P<0.05),心肌梗死程度显著降低(P<0.05),各心功能参数有改善趋势,但差异无统计学意义。结论: iNOS活力增高是心肌缺血再灌注损伤的重要因素,氟伐他汀可降低iNOS活力,降低心肌梗死程度,改善心功能,氟伐他汀75 mg/kg优于10 mg/kg。更多还原

【Abstract】 Objective:To investigate the mechanism of protective effects of fluvastatin on myocardial ischemia-reperfusion injury in hyperlipidemia rabbits. Method:The rabbits were subjected to gastric intralipid perfusion for consecutive 3 weeks to develop models of hyperlipidemia. 40 hyperlipidemia rabbits were randomly divided into 4 groups (10 in each group): IR (ischemia-reperfusion) group, S (sham-operation) group, F10 and F75 group (rabbits received fluvastatin 10 mg/kg or 75 mg/kg by gastric gavage 3 hours before IR). Electrocardiogram and cardiac function were recorded during the experiment. At the end of reperfusion, ischemic myocardium at risk was assessed with Evans blue dye and infarct size by triphenyltetrazolium chloride. Myocardial nitric oxide synthase (NOS) isoenzyme activity was measured with colorimetric method. Result: After ischemia-reperfusion, iNOS activity and myocardial infarct size decreased and cardiac function improved significantly in F10 and F75 groups compared with IR group. iNOS activity was lower and myocardial infarct size was smaller significantly in F75 group than in F10 group. The difference of cardiac function did not reach statistical significance between F10 and F75 groups. Conclusion:The increase of iNOS activity may be one of the important factors in inducing myocardial ischemia-reperfusion injury. The myocardial protection mechanism of fluvastatin may be attributed to its effect on decreasing iNOS activity. Fluvastatin 75 mg/kg may be better than 10 mg/kg in myocardial protection.更多还原