大鼠癫痫持续状态后海马内X-连锁凋亡抑制蛋白及其负性调控因子的表达  

The expression of XIAP, Smac, HtrA2 and XAF1 in the rat hippocampus following status epilepticus

作　　者：李蜀渝[1] 肖波[1] 毕方方[1] 周艳辉[1] 卢晓琴[1] 吴小妹[1] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008

出　　处：《中华神经科杂志》2008年第9期594-597,共4页Chinese Journal of Neurology

基　　金：湖南省科技厅资助项目（06FJ3178）

摘　　要：目的研究大鼠癫痫持续状态（SE）后海马组织中X-连锁凋亡抑制蛋白（XIAP）及其负性调控因子Smac、HtrA2、XAF1的表达变化。方法建立氯化锂-匹罗卡品致痫大鼠SE模型，应用免疫组织化学染色和Western blot方法检测大鼠SE后各时点海马CA3区XIAP、Smac、HtrA2、XAF1及半胱氨酸蛋白酶（caspase）-3蛋白的表达。结果SE后大鼠海马CA3区XIAP蛋白呈弥散性分布于整个神经元内，SE后2h（0．5503±0．0172）起逐渐增高（t=115．87），8h（0．6221±0．0238）达高峰（t=136．69），与对照组（0．1507±0．0165）比较，差异有统计学意义（P〈0．01）。Smac、HtrA2及XAF1蛋白在对照组弱表达，在SE后呈弥散性分布于整个神经元内，2～72h增高。海马CA3区caspase-3活性蛋白在对照组呈阴性，在SE后4～72h明显增高。Western blot发现，SE组各时间点XIAP蛋白表达量与对照组比较差异无统计学意义（P〉0．05），Smac、HtrA2及caspase-3蛋白在对照组很少表达，在SE后2～72h增高（P〈0．01）。结论XIAP及其负性调控因子Smac、HtrA2、XAF1涉及了SE后神经元凋亡的调节，参与了SE后神经元损伤。Objective To investigate the expression of XIAP, Smac, HtrA2 and XAF1 in the hippocampus following SE in rats and to explore the pathophysiological mechanisms of expression of MAP and its negative regulators after SE. Methods The lithium-pilocapine model of status epilepticus was established in SD rat. XIAP, Smac, HtrA2, XAF1 and activated caspase-3 protein were examined using immunohistochemistry. Western blot was used to detect the protein levels of XIAP, Smac, HtrA2 and activated caspase-3. Results XIAP immunoreactivity diffusely distributed within the neuron after SE. Compared with the control group, the expression of CA3 XIAP protein in the SE group was increased gradually since 2 hours （0. 5503±0. 0172 vs 0. 1507±0. 0165, t = 115.87, P 〈0. 01 ）, peaking at 8 hours （0. 6221±0. 0238 vs 0. 1507± 0. 0165, t = 136. 69, P 〈 0.01 ）. The expression of CA3 Smac, HtrA2, XAF1 and activated caspase-3 protein were increased generally following SE. Western blot analysis showed a significant increase in Smac, HtrA2, activated caspase-3 protein levels from 2 to 72 hours following SE, but no significant differences were seen in XIAP protein levels between the control group and the SE group. Conclusions The XIAP, Smac, HtrA2 and XAF1 are involved in the regulation of neuronal apoptosis and implicated in pathophysiological mechanisms of neuronal damage after SE.

关 键 词：癫痫持续状态 海马 X-连锁凋亡抑制蛋白 载体蛋白质类 线粒体蛋白质类 丝氨酸内肽酶类 

分 类 号：R686[医药卫生—骨科学]