MG-132抑制大鼠缺血再灌注心肌细胞凋亡

MG-132 Inhibited Cardiomyocyte Apoptosis of Acute Ischemia-Reperfusion Injury of Rats

目的观察蛋白酶体抑制剂MG-132对急性缺血再灌注大鼠心肌细胞凋亡的影响。方法建立大鼠心肌缺血再灌注模型,治疗组及治疗对照组于再灌注前5min静脉注射MG-132(0.75mg/kg),缺血再灌注组及假手术组注射生理盐水,观察各组心肌组织炎症细胞浸润及心肌细胞凋亡情况。结果MG-132能显著抑制心肌梗死周围组织嗜中性粒细胞的浸润;与缺血再灌注组相比,治疗组核因子κBmRNA水平和蛋白水平显著降低(P<0.05);治疗组再灌注2h、6h及24h亚组凋亡指数较缺血再灌注组同时间点显著下降;与缺血再灌注组相比,Bax的积分光密度值降低(P<0.05),Bcl-2蛋白水平明显上调,Bcl-2/Bax比值显著增加。结论蛋白酶体抑制剂能够抑制急性缺血再灌注心肌的凋亡,具有心肌保护作用。

Aim To probe into the effect of proteasome inhibitor MG-132 on myocytic apoptosis in rat with myocardial ischemia-reperfusion injury. Methods The ischemia-reperfusion model was established after 30 min ligation of left anterior descending （LAD） coronary artery. MG-132 （0.75 mg/kg in 2 mL DMSO） was injected 5 min prior to reperfusion. Electron microscopy, histology, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick end-labeling （TUNEL） method, and reverse transcription-polymerase chain reaction was applied to observe myocardial cell apoptosis. Results Functional effects of MG-132 on polymorphonnuclear neutrophillic leukocytes（PMN） accumulation, activation of nuclear factor kappa B （NF-κB） p65 mRNA and protein levels, and apoptosis were characterized in rat myocardial tissue. MG-132 time-dependently inhibited myocardial p65 mRNA expression and reduced myocardial apoptotic index （AI） after reperfusion for 2 h, 6 h and 24 h （P〈0.01, respectively）. Moreover, MG-132 time-dependently decreased Bax protein levels, while increased Bcl-2 protein levels in ischemic and reperfused myocardium （P〈0.05）, these effects peaked 24 h after reperfusion. Conclusion MG-132 reduced myocardial reperfusion injury by inhibiting myosytic apoptotic cell death and blocking the activation of NF-κB, down-regulating Bax expression and up-regulating Bcl-2 expression as well as elevating Bcl-2/Bax ratio.