辛伐他汀抑制大鼠心肌缺血再灌注时线粒体通透性转换孔开放的研究

Regulation of mitochondrial permeability transition pore by Simvastatin during in vivo ischemia-reperfusion in rat heart

目的探讨调脂药辛伐他汀(Simvastatin)在心肌缺血再灌注损伤中对心肌梗死和心肌缺血面积的影响,及能否抑制线粒体通透性转换孔的开放。方法雄性SD大鼠,随机分为假手术组(Sham)、对照组(Con)、辛伐他汀小剂量组(Sim_1)、辛伐他汀大剂量组(Sim_5)及环孢菌素A组(CsA)。结扎大鼠前降支构建缺血再灌注模型(假手术组除外)。结果 Sim_1、Sim_5及CsA组心肌缺血面积减少分别为26.5%、32.2%及28.6%,各组间差异无统计学意义(P>0.05),但和Con组比较,差异均具有统计学意义(P<0.05)。和对照组比较,各干预组均明显减少Ca2+诱导的mPTP开放(P<0.05);其中,Sim_5组的抑制作用最强,而Sim_1则最弱。结论辛伐他汀能有效的抑制缺血再灌注时心肌细胞mPTP的开放,并能减少缺血再灌注引起的损伤。

Objective To explore the impact of Simvastatin,a lipid lowering agent, on the myocardial infarction and myo- cardial ischemic area, and determine whether it can modulate opening of mitochondrial permeability transition pore （mPTP）. Methods Male SD rats were randomly divided into sham operation group（ Sham）, control group（ Con）, simv- astatin low-dose group（ Sim_l ） , simvastatin high-dose group（ Sim_5 ） and cyclosporine A（CsA）. A rat model of ischemia- reperfusion injury was created by using ligation of the left anterior descending artery （other than the sham-operated group）. Results The myocardial ischemic area reduced significantly in Sim_1, Sim_5 and CsA groups （26.5 % ,32.2% and 28.6% , respectively） as compared to Con group（ P 〈 0.05 ）. Ca2~ -induced mPTP opening was inhibited magnificent- ly in Sim_1 ,Sire_5 and CsA groups as ompared to Con group（P 〈0.05） ,especially in Sire_5 group. Sim_l group showed a minor effect. Conclusion Simvastatin can effectively inhibit mPTP opening and protect the rat heart from ischemia- reperfusion injury.