丙泊酚预处理对大鼠离体心肌浅低温缺血／再灌注损伤后线粒体细胞色素C释放的影响

目的：探讨丙泊酚预处理对大鼠离体心肌浅低温缺血／再灌注（I／R）损伤后心肌细胞凋亡及线粒体细胞色素C释放的影响。方法：应用Langendorff离体心脏灌注模型,取50只SD大鼠随机分为5组：对照组（C组）,二甲基亚砜（DMSO）预处理组（D组）,25、50、100μmol·L^-1丙泊酚预处理纽（P1、P2、P3组）。各组均浅低温缺血55min,再常温灌注60min。D组、P1、P2、P3组在缺血前分别以含DMSO、相应浓度丙泊酚的K-H液灌注10min,再冲洗5min,重复2次。记录平衡灌注末、缺血前即刻、再灌注30、60min时的心功能指标。再灌注60min时测定凋亡细胞,提取心肌线粒体,测定线粒体和胞浆的细胞色素C水平。结果：与C组相比,P3组再灌注30min、60min时左室舒张末压（LVEDP）降低、左室发展压（LVDP）升高（P〈0．05或P〈0．01）;P2、P3组再灌注末心肌细胞凋亡率降低（P〈0．05或P〈0．01）,线粒体细胞色素c释放减少,胞浆细胞色素C的量明显降低（P〈0．05或P〈0．01）。结论：丙泊酚预处理能够通过抑制心肌线粒体细胞色素C释放到胞浆,降低浅低温I／R损伤心肌细胞凋亡率,减轻心肌桶伤．

The effect of propofol preconditioning on cytochrome C release from mitochondria after mild hypothermic ischemia/reperfusion in isolated rat hearts

Aim： To explore the effect of propofol preconditioning on cardiomyocyte apoptosis and cytochrome C release from mitochondria during mild hypothermie ischemia/reperfusion in isolated rat hearts. Methods： 50 isolated SD rat hearts perfused on Langendorff apparatus were randomly divided into 5 groups （ n = 10 ） ： control group（ C ）, DMSO group （D）, 3 different concentrations of propofol groups of 25 μmol· L^-1 （P1）, 50 μmol·L^-1（P2）, 100 μmol·L^-1（P3） propofol respectively. All of the isolated rat hearts were subjected to 31℃ mild hypothennic ischemia for 55 rain followed by 60 rain reperfusion. The D,P1 ,P2,P3 groups were preconditioned by peffusing with K-H solution containing 20μmol·L^-1 DMSO and 25,50,100 μmol·L^-1 propofol respectively for 10 min and then followed by 5 rain K-H solution washing out before ischemia. The preconditioning procedure was repeated twice. Hemedynamics of the hearts was recorded after equilibration（baseline values） immediately before ischemia, 30 rain and 60 min after reperfusion respectively. Cardiomyocyte apoptosis rate and contents of eytosolie and mitochondrial cytoehrome C were measured at the end of reperfusion. Results： After 30 rain and 60 min reperfusion, LVEDP was significantly lower and LVDP was significantly higher in P3 group than those in C group（ P 〈 0.05, P 〈 0.01 ）. Compared with C group, cardiomyoeyte apoptosis rate of the hearts decreased significantly in P2, P3 groups at the end of reperfusion（ P 〈 0.05, P 〈 0.01 ）. Cytochrome C level increased significantly in mitochondria but decreased significantly in cytosol in P2,P3 groups as compared with C group（ P 〈 0.05, P 〈 0.01 ）. Conclusion：Propofol preconditioning decreased cardiomyocyte apoptosis, protected the heart against 31 ℃ mild hypothermic ischemia/repeffusion injury by attenuation of the release of cytochrome C from mitochondria to eytosol.