丙泊酚预处理对大鼠离体心肌缺氧/再给氧损伤线粒体细胞色素C释放的影响  

The effect of propofol preconditioning on cytochrome C release from mitochondria during hypoxia/reoxygenation in isolated rat hearts

作　　者：汪昊星[1] 朱珊珊[1] 曾因明[1] 

机构地区：[1]徐州医学院江苏省麻醉医学研究所.江苏省麻醉学重点实验室

出　　处：《中国药理学通报》2007年第11期1414-1419,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(NoC03030301);江苏省自然科学基金资助项目(No;BK2002139)

摘　　要：目的探讨丙泊酚预处理对大鼠离体心肌缺氧再给氧损伤时心肌细胞凋亡及线粒体细胞色素C释放的影响。方法50只SD大鼠随机分为5组:对照组(C组),DMSO预处理组(D组),25、50、100μmol.L-1丙泊酚预处理组(P1、P2、P3组)。应用Langendorff离体心脏灌注模型,经主动脉用K-H液逆行灌注。各组均缺氧30min,再给氧60min。DMSO组、P1、P2、P3组在缺氧前分别以含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、缺氧前即刻、再给氧30、60min时的心功能指标。再给氧60min时用DNA原位末端缺口标记技术(TUNEL法)测定凋亡细胞,提取心肌线粒体,免疫印迹法测定线粒体和胞质的细胞色素C水平。结果D组与C组相比差异无显著性;与D组相比,P1、P2、P3组再给氧30min、60min时LVEDP降低、LVDP升高(P<0.05),再给氧末心肌细胞凋亡率降低(P<0.05或0.01),心肌线粒体细胞色素C释放减少,胞质细胞色素C的量明显降低(P<0.05或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释放到胞质降低心肌细胞凋亡率,减轻心肌缺氧再给氧损伤。Aim To explore the effect of propofol preconditioning on cardiocyte apoptosis and cytochrome C release from mitochondria during hypoxia/reoxygenation in isolated rat hearts.Methods Fifty male Sprague-Dawley rats weighing 250～300 g were randomly divided into 5 groups（n=10 each）：control group（C）;Dimethyl sulfoxide（DMSO）preconditioning group（D）;3 propofol preconditioning groups with 25 μmol·L-1（P1）、50 μmol·L-1（P2）、100 μmol·L-1（P3）propofol respectively.The isolated rat hearts were retrogradely perfused via aorta with K-H solution on Langendorff apparatus.The isolated hearts were made hypoxia for 30 minutes followed by 60 minutes reoxygenation in each group.The D,P1,P2,P3 groups were preconditioned by perfusing 10 min K-H solution containing 20 μmol·L-1 DMSO and 25,50,100 μmol·L-1 propofol respectively and then followed by 5 min K-H solution reperfusion before hypoxia.The preconditioning procedure was repeated twice.The cardiac functional variables were recorded after equilibration（baseline values）,immediately before hypoxia,at the end of 30 min and 60 min reoxygenation.Apoptotic myocardial cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling（TUNEL）and the level of cytochrome C expression in myocardial cytosol and mitochondria was measured by Western blot at the end of reoxygenation.Results At the end of 30 min and 60 min reoxygenation,LVEDP was significantly lower and LVDP was significantly higher in P1,P2,P3 groups than in D group（P〈0.05）.Apoptosis rate decreased significantly in P1,P2,P3 groups than in D group at the end of reoxygenation（P〈0.05 or 0.01）.Cytochrome C level increased significantly in mitochondria but decreased significantly in cytosol in P1,P2,P3 groups as compared with D group（P〈0.05 or 0.01）.There was no significant difference between D group and C group.Conclusions Propofol preconditioning can decrease cardiocyte apoptosis and protect the heart against hypoxia/reoxygenation injury by it

关 键 词：丙泊酚预处理 缺氧再给氧损伤 凋亡 细胞色素C 

分 类 号：R332[医药卫生—人体生理学] R322.11[医药卫生—基础医学]