异丙酚对大鼠心肌缺血/再灌注损伤时NF-κB活化和细胞凋亡的影响

目的:观察异丙酚对大鼠心肌缺血/再灌注时核因子-κB(NF-κB)的活化和细胞凋亡的影响,以探讨异丙酚的心肌保护作用机制。方法:采用阻断大鼠左冠状动脉前降支30min,再灌注2h心肌缺血/再灌注损伤模型。60只SD大鼠随机分为假手术组(Sham)、缺血/再灌注组(I/R)和异丙酚3、6、12mg/(kg.h)组。光、电镜观察心肌组织的形态学变化。免疫组化染色分析心肌组织中NF-κB的核移位,Western blot检测心肌组织NF-κB和caspase-3的表达。原位末端标记(TUNEL)检测心肌细胞凋亡。结果:I/R组心肌纤维排列紊乱,心肌细胞水肿;线粒体膜肿胀,嵴排列紊乱甚至溶解消失。与I/R组相比,6,12mg/(kg·h)组异丙酚组心肌损伤明显减轻。与Sham组相比,I/R组NF-κB活化,明显从细胞浆移位于细胞核,表达量也显著增加(P0.05);心肌caspase-3表达增强(P0.01),心肌细胞凋亡指数升高(P0.05)。而异丙酚6mg/(kg·h)、12mg/(kg·h)组,NF-κB从细胞浆向细胞核的移位被明显限制,NF-κB的表达量也明显低于I/R组(P均0.05);心肌caspase-3表达减弱,心肌细胞凋亡指数减少(与I/R组相比,P0.05)。结论:异丙酚的心肌保护作用可能与其抑制NF-κB的活化,下调caspase-3的表达,从而抑制心肌细胞凋亡有关。

Effects of propofol on the activation of nuclear factor-kappaB and cardiomyocytes apoptosis during myocardial ischemia/reperfusion injury in rats

Objective： To explore the molecular mechanisms of propnfol in myocardial protection, the activation of nuclear factor-feB （NF-κB） and the apoptosis of eardiomyoeytes were examined. Methods： Rat myocardium I/R injury was induced by occluding the left main eornnary artery for 30 min and reperfusing for 2 h. Propofol was intravenously given 15 min before isehemia. The pathological changes of myoeardium were examined by light and electron microscopy. The translocation of NF-κB in the cardiomyoeytes was detected by immunohistoehemistry. The expressions of NF-κB and caspase-3 were determined by Western blot. The incidence of cardiomyoeyte apoptosis was detected by the TdT- mediated dUTP nick end labeling （TUNEL） staining. Results： The pathological changes of myocardium induced by L/R injury such as cardiomyocyte swelling, myofibrillar lysis, disorganized, mitochondrial membrane swelling, and the eristae disruption were significantly alleviated by 6, 12 mg/（ kg·h） propofol. Compared with the sham control group, NF-κB significantly transloeated from the cytoplasm into the nucleus in the I/R group. And the expression of NF-κB in the nuclei markedly increased （P 〈 0.05）. In addition, the expression of easpase-3 mad the apoptosic index were significantly increased in the I/R group （ P 〈 0.05）. Compared with those of I/R group, administration of propofol at 6, 12 mg/（ kg·h） significantly inhibited the NF-κB translocation into nucleus and attenuated the expression of NF-κB in the nuclei （P 〈 0. 05）, decreased the expression of easpase-3 in myocardium （P 〈 0.05） and inhibited the occurrence of cardiomyocytes apoptosis. Conclusion： Propofol could inhibit NF-κB activation and down-regulate the expression of easpase-3 and as a result suppress cardiomyocytes apoptotic initation during the myocarditan 1/R injury, which may be one of the molecular mechanisms of its eardioproteetion.