CART阻抑对阿尔茨海默病大鼠记忆能力的影响Effect of CART inhibition of memory ability of Alzheimer's disease rats
刘伟;常娜;潘昊君;李昕;
摘要(Abstract):
目的探讨可卡因苯丙胺调节转录肽(CART)对阿尔茨海默病(AD)大鼠脑内β淀粉样蛋白(Aβ)生成和Tau蛋白磷酸化的影响。方法实验分为4组,依次为模型组(AD大鼠)、实验组(AD模型大鼠尾静脉注射CART)、假手术组(用等量的PBS代替Aβ_(1-40))、对照组(正常饲养)。脑侧室注射Aβ_(1-40)构建AD大鼠模型,Morris水迷宫检测各组大鼠逃避潜伏期和穿越平台次数,ELISA法检测脑组织中Aβ_(1-40)水平,RT-PCR检测脑组织中胰岛素降解酶(IDE)、中性内肽酶(NEP)、低密度脂蛋白受体相关蛋白(LRP-1)水平,Western blot检测脑组织中Tau蛋白磷酸化、IDE、LRP-1、NEP、糖原合成激酶3β(GSK-3β)、p-GSK-3β水平。结果实验组大鼠逃避潜伏期明显低于模型组,而穿越平台次数明显高于模型组。实验组大鼠Aβ_(1-40)水平、Tau 5水平、Tau磷酸化水平(Tau pSp(199/202)、Tau(199/202)、Tau(pT231))、GSK-3β、p-GSK-3β明显低于模型组,而IDE、LRP-1、NEP明显高于模型组。结论CART能够通过调节IDE、LRP-1、NEP水平降低AD大鼠模型中Aβ_(1-40)水平,能够通过调节GSK-3β抑制Tau蛋白磷酸化,进而改善AD大鼠的记忆能力。
关键词(KeyWords): 阿尔茨海默病;β淀粉样蛋白;Tau蛋白;记忆能力;可卡因苯丙胺调节转录肽
基金项目(Foundation): 2014年河南省医学科技攻关计划重点项目,编号:201402018
作者(Authors): 刘伟;常娜;潘昊君;李昕;
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