二氮嗪预处理对缺氧复氧后大鼠海马神经元凋亡的影响  

Effects of diazoxide preconditioning on anosda-reoxygenation induced apoptosis in rat hippocampai neurons

作　　者：汪炜健[1] 刘荣国[1] 史春霞[1] 李立环[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京阜外心血管病医院麻醉科

出　　处：《中华麻醉学杂志》2006年第3期252-254,共3页Chinese Journal of Anesthesiology

基　　金：教育部博士点基金资助项目(20030023028)

摘　　要：目的研究线粒体内膜ATP敏感性钾通道(Mito-KATP)特异性开放剂二氮嗪预处理对缺氧复氧后大鼠海马神经元凋亡的影响。方法取离体培养的大鼠海马神经元,随机分为4组:对照组 (A组)、二氮嗪30／μmol/L组(B组)、二氮嗪100 μmol/L组(C组)、二氮嗪100 μmol/L+Mito-KATP特异性阻断剂5-羟葵酸100μmol/L组(D组),各组神经元每天给予相应药物预处理1 h,连续3 d,继而缺氧4 h 复氧24 h,观察神经元的活力、凋亡率、Bax和Bcl-2蛋白的表达水平。结果与其它3组比较,C组海马神经元活力增强,凋亡率降低,Bcl-2蛋白表达水平升高,Bax蛋白表达水平下降(P<0．01)。结论 100μmol／L二氮嗪预处理通过改善Bcl-2与Bax蛋白表达的失衡,降低神经元的凋亡,对大鼠海马缺氧复氧神经元产生了保护效应。Objective To determine what effects diazoxide, a selective opener of mitochondrial ATP- sensitive potassium channel （Mito-KATv）, exerts on apoptosis in hippocampal neurons caused by anoxia- reoxygenation. Methods Newborn SD rots （ 〈 24 h after birth） weighing 5-6 g were decapitated and hippocampal tissue was isolated and hippocampal neurons were prepared by digestion with trypsin. After being cultured for 9-10 days the hippocampal neurons were randomly assigned to one of 4 groups： diazoxide 0, 30, 100 μmol/L（group A, B, C） and diazoxide 100μmol/L ＋ 5-hydroxydecanoate 100 μmol/L （group D）. The hippocampal neurons were treated with diazoxide lh per day for 3 days before being subjected to 4h oxygen deprivation followed by reoxygenatian. The neuronal vitality was assayed and apoptosis rate determined after 24 h reoxygenation. The expression of Bcl-2 and Bax protein was determined by western blotting. Results The neuronal survival rate was significantly higher and apoptosis rate significantly lower in group C （ diazoxide 100 μmol/L ） than in other 3 groups （ P 〈 0.01 ） through up-regulation of Bcl-2 expression and down-regulation of Bax expression. Conclusion Preconditioning with diazoxide 100 μmol/L can protect hippocampal neurons against anoxia-reoxygenation injury by attenuating neuronal apoptosis.

关 键 词：二氮嗪 细胞凋亡 细胞低氧 海马 神经元 

分 类 号：R96[医药卫生—药理学]