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
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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)


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

    Abstract:

    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 N-terminal 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.

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李小翠,王晓天,张清秀,尤红娟,周 峰,汤仁仙,郑葵阳,刘晓梅. 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[J].南京医科大学学报(自然科学版),2014,(10):1329-1332

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  • 收稿日期:2014-06-14
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  • 在线发布日期: 2014-11-02
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