2,6-二异丙基苯酚逆转嗅球切除抑郁模型大鼠电休克后的Tau蛋白过度磷酸化和认知障碍  

2,6-Diisopropylphenol Protects Against The Impairment of Learning-memory and Reduces The Hyperphosphorylation of Protein Tau Induced by Electroconvulsive Shock in The Depression Model Rats Whose Olfactory Bulbs Were Removed

作　　者：刘超[1] 闵苏[1] 魏柯[1] 刘东[2] 董军[1] 罗洁[1] 刘小滨[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科,重庆400016 [2]天津医科大学第二医院神经外科,天津300211

出　　处：《生物化学与生物物理进展》2012年第9期893-909,共17页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金面上资助项目(30972831)~~

摘　　要：通过观察2,6-二异丙基苯酚对电休克后嗅球切除抑郁模型大鼠学习记忆和Tau蛋白过度磷酸化的影响,探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠学习记忆的影响,为改善学习记忆障碍的神经心理学机制研究和临床干预性治疗提供实验依据.按随机单位组2×2析因设计设置2个干预因素,即电休克干预(两水平:无处置、施行一个疗程电休克)和2,6-二异丙基苯酚干预(两水平:腹腔注射5 ml生理盐水或5 ml 2,6-二异丙基苯酚100 mg/kg)的所有组合.选24周龄健康雄性Sprague-Dawley大鼠建立嗅球切除抑郁模型,将32只24周龄模型大鼠随机分为4个实验组(n=8):Ⅰ组(腹腔注射5 ml 2,6-二异丙基苯酚100 mg/kg)、Ⅱ组(腹腔注射5 ml 2,6-二异丙基苯酚100 mg/kg+施行电休克1个疗程)、Ⅲ组(腹腔注射5 ml生理盐水)、Ⅳ组(腹腔注射5 ml生理盐水+施行电休克1个疗程).全部电休克处置结束24 h内开始Morris水迷宫检测,之后留取海马组织.高效液相色谱法检测神经递质谷氨酸(Glu)在海马组织中的含量;免疫组化SP法和蛋白质印迹法检测Tau-5(总Tau蛋白)、p-PHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262、GSK-3β1H8和PP-2A在海马组织神经元中的表达.电休克和2,6-二异丙基苯酚均可造成大鼠学习记忆障碍,即延长逃避潜伏期并缩短空间探索时间,两者的影响呈相减效果.电休克可明显增加海马中神经递质谷氨酸(Glu)的浓度,2,6-二异丙基苯酚可降低海马中神经递质Glu的浓度,且两者有相减效果.电休克和2,6-二异丙基苯酚对海马总Tau蛋白和PP-2A蛋白的表达无明显影响.电休克可增加海马中磷酸化Tau蛋白和GSK-3β1H8蛋白的表达;2,6-二异丙基苯酚可减少海马中磷酸化Tau蛋白和GSK-3β1H8蛋白的表达;两者的影响均呈相减效果.实验结果表明,电休克导致海马Glu浓度升高,通过上调GSK-3β1H8增加海马Tau蛋白的磷酸化程度导致�Protein Tau is a very unequal phosphoric microtubule associated protein, which affect the transport of substances in the axons of the neurons, whose phosphorylation is one of the key methods to regulate neuronal function. The hyperphosphorylation of protein Tau can damage the learning and memory of rats. The impairment of learning-memory induced by electroconvulsive shock in depressed rats is relevant to the function failure of glutamic acid signal system. The phosphorylation of protein Tau can be up-regulated by the individual stress level through the excitatory neurotransmission system. The mechanisms of 2, 6-diisopropylphenol effect on the central nerve system relate to inhibiting the release of glutamic acid and the activity of NMDAR. And the 2, 6-diisopropylphenol can protects against the impairment of learning-memory induced by electroconvulsive shock in depressed rats though inhibiting the excitotoxicty of glutamate. The rise of glutamic acid which induced by electroconvulsive shock in depressed rats can lead to the impairment of learning-memory through up-regulating the hyperphosphorylation of protein Tau？ The 2, 6-diisopropylphenol can protect against this process？ This study explore the reversion of the 2, 6-diisopropylphenol against the impairment of learning-memory and the hyperphosphorylation of protein Tau induced by electroconvulsive shock in depressed rats, in order to provide experimental evidence for neuropsychological mechanisms on improving learning and memory and the clinical intervention treatment. According to the design of factorial analysis, two intervention factors were set up： the electroconvulsive shock （two levels： no disposition; a course of electroconvulsive shock） and the 2, 6- diisopropylphenol （two levels： 5 ml Saline was injected peritoneally; 5 ml 2, 6-diisopropylphenol was injected peritoneally by dosage of 100 mg/kg）. Thirty-two adult depression model rats whose olfactory bulbs were removed were randomly divided into four experimental groups （n=8, in each

关 键 词：2 6-二异丙基苯酚 电休克 学习记忆能力 TAU蛋白 过度磷酸化 糖原合成酶激酶-3Β 

分 类 号：R395.1[哲学宗教—心理学] R749.054[医药卫生—医学心理学]