AKT及JNK激酶在大鼠脑缺血预处理后线粒体中的表达  

Expressions of AKT and JNK in mitochondria after cerebral ischemic precondition in rats

作　　者：张颖[1,2] 王瑞敏[1] 刘斌[2] 杨丽彩[1] 黎洁[1] 张晋霞[2] 李世英[2] 

机构地区：[1]华北煤炭医学院实验研究中心,河北唐山063000 [2]华北煤炭医学院附属医院神经内科,河北唐山063000

出　　处：《第四军医大学学报》2009年第23期2742-2745,共4页Journal of the Fourth Military Medical University

基　　金：河北省自然科学基金(C2008000997;C2008000994);河北省教育厅自然科学基金(2008140)

摘　　要：目的:观察脑缺血预处理后大鼠海马CA1区神经元线粒体内JNK和AKT的激活,并使用AKT,JNK抑制剂进一步探讨其对线粒体结构功能的影响.方法:制作大鼠四动脉结扎脑缺血模型,Western Blot方法分析海马CA1区线粒体内AKT,JNK的磷酸化水平和蛋白表达,利用透射电子显微镜技术观察海马CA1区超微结构.结果:Western Blot结果显示p-AKT于缺血再灌注30 min达高峰,而预处理后再灌注6 h开始升高,1,3 d达高峰.JNK在缺血后再灌注30 min和3 d呈现两个激活高峰,而预处理后再灌注6 h显著升高,1,3 d明显低于正常组,且与缺血再灌注相同时间点相比显著降低.AKT,JNK的蛋白表达无明显变化.透射电子显微镜观察显示正常组及溶剂对照组神经元超微结构无明显变化,缺血组与AKT抑制剂组可见大量神经元损伤,与缺血组相比预处理组及JNK抑制剂组神经元损伤显著减轻.结论:脑缺血预处理可诱导AKT,JNK在海马CA1区线粒体内的差异激活,并通过增强AKT活性、抑制JNK磷酸化而保护线粒体的结构和功能,从而保护缺血性神经元.AIM：To investigate the activation of AKT or JNK in neural mitochondria in hippocampal CA1 region of the rats,as well as the effect on mitochondria functional role following cerebral ischemic precondition.METHODS：Transient brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats.Phosphorylation level and the protein expression of AKT or JNK in mitochondria of hippocampus CA1 region were investigated using Western Blot analysis,neurologic morphology changes were observed under transmission electron microscope.RESULTS：Western Blot analysis showed that during ischemia/reperfusion,AKT activation immediately increased with a peak at 30 min.In contrast,in CIP groups AKT activation increased at 6 h then reached its peaks at 1 and 3 d of reperfusion.On the other hand,JNK activation significantly increased at 30 min of reperfusion and then decreased without CIP.While during the later phase of refusion（6 h-3 d）,the level of p-JNK gradully increased,which was paralleled by decrease the JNK activation with CIP.Under those conditions,the protein expressions AKT and JNK had no significant change.The cellular ultrastructure was normal in sham group and vehicle group under transmission electron microscope.A lot of neural cells loss and damaged ultrastructure were found either in ischemia or AKT inhibitor group in hippocampal CA1 region.Comparatively,this damage was weaken in CIP groups and JNK inhibitor groups.CONCLUSION：Cerebral ischemia preconditioning caused different activation of JNK and AKT in neural mitochondria of hippocampal CA1 region.In more exactly way,CIP protected ultrastructure and function of mitochondria in hippocampal neurons from ischemic injury through enhancing the activation of AKT and inhibiting the expression of p-JNK.

关 键 词：缺血预处理 JNK AKT 线粒体 海马 

分 类 号：R54[医药卫生—心血管疾病]