异丙酚预处理对大鼠肝缺血再灌注后线粒体膜通透性转换孔的影响  

Effect of propofol pretreatment against hepatic ischemia-reperfusion injury on mitochondrial perme. ability transition pore in rats

作　　者：赵鸽[1] 申新[1] 朱宇麟[1] 王强[1] 吕毅[2] 

机构地区：[1]西安交通大学第一附属医院麻醉科,710061 [2]西安交通大学第一附属医院肝胆外科,710061

出　　处：《中华肝胆外科杂志》2017年第7期468-473,共6页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金（81670572）;陕西省科学技术攻关项目（2014K11-03-03-08）

摘　　要：目的探讨异丙酚预处理对大鼠肝缺血再灌注（I／R）后线粒体膜通透性转换孔（MPTP）的影响以及糖原合成酶激酶-3p（GSK-3p）的作用机制。方法将30只SD大鼠随机分为5组（n=6）：假手术组（S组）、缺血再灌注组（I／R组）、环孢素A（CsA）预处理组（C组）、异丙酚预处理组（P组）和苍术苷＋异丙酚预处理组（A＋P组）。采用Nauta大鼠肝热缺血再灌注模型。热缺血60min后开放动脉夹，再灌注120min。P组于肝缺血前30min经股静脉泵注异丙酚12mg／（kg·h）至缺血末。CsA组于肝缺血前20min经股静脉注射CsA2mg／kg。A＋P组给予异丙酚前10min经股静脉注射苍术苷20μmol／kg，然后行异丙酚预处理，再行I／R。各实验组于再灌注末处死大鼠，抽取肝上下腔静脉血，收集肝左叶相同部位肝脏缺血组织待用。结果与S组比较，I／R组和A＋P组ALT、AST血清水平明显升高，肝细胞线粒体肿胀程度明显增加，线粒体膜电位明显降低；肝细胞胞质Caspase-3表达明显升高，肝细胞凋亡明显增加，肝细胞胞质p-GSK-3BSer^9表达明显降低。与I／R组比较，P组和C组ALT、AST血清水平明显降低、肝细胞线粒体肿胀程度减轻、线粒体膜电位明显增加；肝细胞胞质Caspase-3表达明显降低，肝细胞凋亡明显降低，肝细胞胞质p-GSK-3βSer^9表达明显升高。P组和C组两者ALT、AST、肝细胞线粒体肿胀程度、线粒体膜电位水平、肝细胞凋亡、肝细胞胞质Caspase-3和p-GSK-3βSer^9表达差异均无统计学意义。结论异丙酚预处理能够明显减轻大鼠肝缺血再灌注损伤。其作用机制可能是通过抑制GSK-3β活性、增加p-GSK-3βSer^9、抑制肝细胞MPTP开放、减轻肝细胞凋亡而实现的。Objective To investigate the protective effect of propofol against hepatic ischemia- reperfusion injury in rats on mitochondrial permeability transition pore （MPTP） and the mechanism of GSK- 3β. Methods Thirty SD rats were randomly assigned into five groups（n =6） ： sham operation group （S group）, ischemia reperfusion group （I/R group）, CsA pretreatment group （C group）, propofol pretreatment group （P group）, and propofol plus atractyloside pretreatment group （A ＋ P group）. Nauta liver ische- mia-reperfusion rat model was used. Liver lobes were subjected to warm ischemia for 60min and then reperfusion for 120 min. In P group, propofol [ 12 mg/（ kg · h） ] was administered in the femoral vein for 30 min before ischemia until the end of reperfusion. In C group, CsA （2 mg/kg） was administered in the femoral vein for 20min before ischemia. In A ＋ P group, 20 μmol/kg of atractyloside was given through the femoral vein 10rain before the injection of propofol. Rats were sacrificed at the end of reperfusion, and venous blood and hepatic tissue specimens from the same part of ischemia were obtained from different groups. Results Compared with S group, the AST and ALT levels were increased significantly, mitochondrial swelling were increased and mitochondrial membrane potential were decreased significantly in I/R group and A ＋ P group. Casepase-3 were increased significantly and p-GSK3β Ser9 were decreased significantly in I/R group and A ＋ P group. Compared with I/R group, the content of AST and ALT were decreased significantly, mito- chondrial swelling were decreased and mitochondrial membrane potential were increased significantly, case- pase-3 release were decreased significantly and p-GSK3 β Ser9 were increased significantly in P group and C group. GSK-3β in each group displayed no significant difference. Conclusions Propofol can significantly reduce hepatic ischemia-reperfusion injury. The protective effect of propofol may be achieved via the inhibition of GSK-3β acti

关 键 词：异丙酚 缺血再灌注损伤 线粒体膜通透性转换孔 凋亡 

分 类 号：R614[医药卫生—麻醉学]