AMP激活的蛋白激酶对大鼠弥漫性轴索损伤后神经元自噬的调节  

Role of AMP-activated protein kinase in neuronal autophagy after diffuse axonal injury in rats

作　　者：孙鹏[1] 宋锦宁[1] 马旭东[1] 李丹东[1] 赵永林[1] 安吉洋[1] 张明[1] 庞宏刚[1] 

机构地区：[1]西安交通大学医学院第一附属医院神经外科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2015年第1期34-39,53,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.30471774);教育部新世纪优秀人才支持计划资助项目(No.NCET-05-0831);陕西省自然科学基金资助项目(No.2003C1-16)~~

摘　　要：目的研究AMP激活的蛋白激酶(AMPK)信号通路在弥漫性轴索损伤(DAI)大鼠脑组织中的表达,探讨AMPK对DAI后神经自噬的调节机制。方法大鼠头颅瞬间旋转损伤法建立DAI模型,免疫蛋白印迹法检测造模后1、3、7d大脑皮层和海马AMPK、磷酸化AMPK(p-AMPK)、Beclin1、LC3Ⅰ/Ⅱ、p62蛋白的动态表达,并与正常组和假手术组比较。侧脑室给予AMPK抑制剂Compound C及激活剂AICAR,检测药物干预对大鼠神经自噬相关蛋白表达的影响,并与DAI组和vehicle组进行比较。结果与正常组和假手术组相比,DAI 1d后脑内AMPK信号通路激活,3d后脑内自噬水平上调;Compound C可以减少AMPK磷酸化激活同时下调脑内的自噬水平,AICAR可以增高AMPK磷酸化水平上调神经自噬改善神经功能损伤。结论大鼠DAI后AMPK的激活可以上调神经自噬的水平,对DAI后的神经保护有重要意义。Objective To investigate the activation of AMP-activatcd protein kinase （AMPK） in the cerebral cortex and the hippocampus after diffuse axonal injury （DAI） so as to explore the role of AMPK in neuronal autophagy after DAI. Methods Rat diffuse axonal injury was induced by a new experimental facility, which was developed to make the rat head spin 90 degrees at the moment to cause shearing injury. Western blot was used to detect the protein levels of phosphorylated AMPK and autophagy-related protein （Beclinl, LC3 1/I｜ , p62） in the cerebral cortex and the hippocampus. After AICAR and Compound C were administered by intraventricular injection, the change of p-AMPK level was examined, and the effects of AICAR and Compound C on neurological behavior and the expression of Beclinl were observed. Results Compared with those in normal group and sham- operation group, the expression of phosphorylated AMPK and the level of neural autophagy were up-regulated sharply after DAI; A1CAR administration facilitated neuronal autophagy and ameliorated neurological deficit through upregulating phosphorylated AMPK. In contrast, Compound C treatment downregulated the phosphorylated level of AMPK and the expression of Beclinl. Conclusion The activation of AMPK up-regulates the level of ncural autophagy, which is important to neural protection after DAI.

关 键 词：弥漫性轴索损伤 AMP激活的蛋白激酶 自噬 大鼠 颅脑损伤 

分 类 号：R651.15[医药卫生—外科学]