异丙酚和氯胺酮减轻电休克诱发的认知障碍  

Propofol and Ketamine reduces electroconvulsive shockinduced impairment of learning-memory

作　　者：李利彪[1] 刘超[2] 闵苏[3] 刘万富[4] 古妙宁[1] 

机构地区：[1]南方医科大学南方医院麻醉科,广东广州510515 [2]天津市胸科医院麻醉科,天津300222 [3]重庆医科大学附属第一医院麻醉科,重庆400016 [4]中国人民解放军南京军区福州总医院麻醉科,福建福州350025

出　　处：《中国现代医学杂志》2014年第29期1-7,共7页China Journal of Modern Medicine

基　　金：国家自然科学基金(No:30972831);博士后科学基金(No:2013M530880)

摘　　要：目的该文通过观察异丙酚和氯胺酮对电休克(ECT)后WKY大鼠认知和Tau蛋白过度磷酸化的影响,探讨异丙酚和氯胺酮对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠认知的影响。方法采用随机单位组析因设计2个干预因素,即电休克干预(2水平:无处置、施行1疗程ECT)和异丙酚、氯胺酮干预(3水平:注射生理盐水、异丙酚、氯胺酮)的所有组合(2×3析因设计)进行实验。全部ECT处置结束24 h内开始Morris水迷宫检测,然后留取各组大鼠海马组织。高效液相色谱法检测海马组织中神经递质Glu含量;Western blot检测Tau 5(总Tau蛋白)、p-PHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262在海马组织中的表达。结果 ECT和实验药物均可造成大鼠认知障碍,即延长逃避潜伏期并缩短空间探索时间;ECT和实验药物合用之后,其造成的大鼠认知障碍程度反而减轻。ECT可增加海马中磷酸化Tau蛋白的表达;异丙酚和氯胺酮可使电休克造成的海马磷酸化Tau蛋白的表达增加的幅度降低。结论异丙酚和氯胺酮可使ECT造成的海马磷酸化Tau蛋白的表达增加的幅度降低,从而改善ECT后的认知障碍。【Objective】 To explore the effect of Propofol and Ketamine on the impairment of learningmemory and the hyperphosphorylation of tau protein induced by electroconvulsive shock in depressed rats.【Methods】The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock（two levels： no disposition; a course of ECT） and the excitatory amino acid receptor antagonists（three levels： iv saline; iv Propofol; iv Ketamine）. Forty-eight adult WKY rats were randomly divided into six experimental groups. The Morris water maze test started within 1 day after the finish of the course of ECT. The hippocampus was removed. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau 5, p-PHF1Ser396/404,p-AT8Ser199/202 and p-12E8Ser262 in the hippocampus of rats were detected by Western blotting. 【Results】 The results showed that ECT and the experimental drugs induced the impairment of cognitive ability in depressed rats. ECT up-regulated the hyperphosphorylation of tau protein, while the experimental drugs down-regulated it. 【Conclusion】 ECT up-regulates the content of glutamate, which up-regulates the hyperphosphorylation of tau protein which results in the impairment of cognitive ability in depressed rats.

关 键 词：异丙酚 氯胺酮 电休克 认知能力 TAU蛋白 过度磷酸化 

分 类 号：R-332[医药卫生]