表没食子儿茶素没食子酸酯对APP/PS1转基因小鼠认知功能和海马自噬的影响

目的探讨表没食子儿茶素没食子酸酯(EGCG)对APP/PSl转基因小鼠海马神经元自噬的作用。方法8月龄APP/PSl转基因小鼠随机分为模型组(Tg)、EGCG低剂量组(Tg/EGCG-L)、高剂量组(Tg/EGCG-H),同月龄C57BL/6J小鼠作为对照组(NT)。采用Morris水迷宫检测各组小鼠学习、记忆能力;Western blot检测各组小鼠海马ULK1、P62、LC3Ⅱ/LC3Ⅰ的蛋白表达;免疫组织化学方法检测mTOR的表达;ELISA法检测Aβ1-42水平。结果与NT组比较,Tg组小鼠寻找平台的逃避潜伏期延长及穿越目的象限的次数减少(P<0.05),海马ULK1表达降低、P62、LC3Ⅱ/LC3Ⅰ、Aβ1-42表达升高(P<0.05),EGCG治疗组较Tg组各异常指标均明显改善(P<0.05)。结论EGCG可以改善APP/PSl小鼠空间学习记忆能力,其机制可能与提高海马神经元自噬活性,减少脑内Aβ沉积有关。

Effects of epigallocatechin-3-gallate on cognitive function and hippocampal autophagy in APP/PSl transgenic mice

Aim To explore mechanism of epigallocatechin-3-gallate(EGCG)on alleviation of hippocampal neuronal autophagy in APP/PSl transgenic mice.Methods 8-month old APP/PS1 transgenic mice were randomly divided into three groups:model group(Tg),EGCG low dose group(Tg/EGCG-L),high dose group(Tg/EGCG-H).C57BL/6J mice were utilized as control.Learning and memory were detected by Morris water maze test.The hippocampal ULK1,P62,LC3Ⅱ/LC3Ⅰ,mTOR and Aβ1-42 expressions were detected by Western blot,immunohistochemical staining and ELISA.Results Compared with NT mice,Tg mice showed a marked prolongation of the escape latency in MWM test(P<0.05).Decreased ULK1 expression and increased P62,LC3Ⅱ/LC3Ⅰand Aβ1-42 were detected(P<0.05).EGCG-treated group showedmarked improvement of all these abnormal changes(P<0.05).Conclusions EGCG treatment is able to improve cognitive function,which may be attributed to ameliorated autophagic networks dysfunction and reduced Aβplaques in the the hippocampi of APP/PSl transgenic mice.