MLK3信号通路在癫痫及脑缺血海马CA3区神经元中的不同作用  

Effects of MLK3 pathway on neuron from hippocampal CA3 region in epilepsy and ischemia model

作　　者：李小翠[1] 王晓天[1] 张清秀[2] 尤红娟[1] 周峰[1] 汤仁仙[1] 郑葵阳[1] 刘晓梅[1] 

机构地区：[1]徐州医学院基础学院,江苏徐州221004 [2]徐州医学院第二附属医院神经科,江苏徐州221002

出　　处：《南京医科大学学报（自然科学版）》2014年第10期1329-1332,共4页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81301120);江苏省高校自然科学基金(13KJB320027);徐州医学院院长专项人才基金(2012KJZ10)

摘　　要：目的:研究混合性谱系激酶3(MLK3)信号通路对癫痫及脑缺血海马CA3区神经元的作用。方法 :采用海人藻酸(KA)或四动脉结扎法分别建立大鼠癫痫及全脑缺血模型,运用免疫印迹技术检测在KA注射后及脑缺血再灌注后不同时间海马CA3区MLK3和c-Jun的N端激酶(JNK)的活化水平;采用焦油紫染色,观察大鼠海马CA3区神经元的损伤。结果:KA刺激6 h,癫痫大鼠海马CA3区MLK3和JNK明显激活,1 d后仍维持在较高水平(P<0.05);MLK3和JNK的总蛋白表达并无显著改变。脑缺血大鼠海马CA3区,缺血再灌注后各时间点,MLK3和JNK并未出现明显的活化。此外,大鼠致痫后7 d,海马CA3区神经元大量死亡;缺血再灌注后7 d,海马CA3区神经元并未受到明显损伤。结论:MLK3/JNK信号通路参与了癫痫脑损伤海马CA3区神经元的损伤;但并未介导缺血性脑损伤海马CA3区神经元的存活。Objective：To study the effects of mixed-lineage kinase 3（MLK3） signaling pathway on neuron from hippocampal CA3 region in epilepsy rats and ischemia rats. Methods：Seizure models and cerebral ischemia models were induced by kainic acid（KA）and four-vessel occlusion in SD rats,respectively. Immunoblotting was performed to examine the activation of MLK3 and c-Jun Nterminal kinase（JNK） at different times after KA injection and ischemia-reperfusion（I / R） in hippocampal CA3 regions,respectively.The neuronal survival in hippocampal CA3 regions was observed by cresyl violet staining both in epilepsy rats and ischemia rats.Results：The phosphorylation of MLK3 and JNK in cytoplasm increased rapidly at 6 h after KA injection than those in the saline group,and still was in higher level at 1 d in hippocampal CA3 region（P 〈 0.05）. Total protein expression of MLK3 and JNK showed no significant change. However,the expression of p-MLK3 and p-JNK showed no obvious changes at different time after reperfusion in hippocampal CA3 region. Furthermore,a large number of neurons were loss in hippocampal CA3 region at 7 d after KA injection.Correspondingly,no obvious neuronal damages were found in hippocampal CA3 regions at 7 d after reperfusion. Conclusion：MLK3 /JNK signaling pathway plays an important role in neuronal cells death in hippocampal CA3 region in epilepsy rats,however,MLK3 /JNK pathway does not mediate the neuronal survival in hippocampal CA3 region in ischemia rats.

关 键 词：癫痫 脑缺血再灌注 海马CA3区 MLK3 JNK 

分 类 号：R742.1[医药卫生—神经病学与精神病学]