EGCG改善D-gal诱导阿尔茨海默病模型大鼠认知障碍机制研究

被引:5
作者
姚维范
刘明妍
钟欣
王崴
杜可
杨时伦
毛瑞琨
魏敏杰
机构
[1] 中国医科大学药学院药理学教研室
关键词
EGCG; p75NTR通路; 凋亡; 认知障碍; D-gal诱导AD模型大鼠;
D O I
10.16680/j.1671-3826.2016.06.07
中图分类号
R749.16 [];
学科分类号
摘要
目的探讨表没食子儿茶素没食子酸酯(EGCG)通过抑制p75NTR介导的凋亡通路相关因子改善D-gal诱导阿尔茨海默病(AD)模型大鼠学习记忆障碍的作用及其机制。方法以Morris水迷宫观察动物行为学变化,TUNEL法检测神经细胞凋亡情况,同时采用免疫组化及Western blot法检测其脑内Cleaved-Caspase-3表达水平,并用Western blot法检测p75NTR介导的凋亡通路相关蛋白表达水平。结果 EGCG明显改善D-gal诱导AD模型大鼠学习记忆障碍,抑制其脑内TUNEL阳性细胞表达,降低凋亡特征性蛋白Cleaved-Caspase-3的表达水平。同时,EGCG可通过抑制p75NTR介导的凋亡相关通路,显著降低p75ICD表达水平及其下游JNK2、c-Jun磷酸化水平,降低下游凋亡相关蛋白p53的表达水平,从而发挥抗凋亡、改善学习记忆障碍的抗AD作用。结论 EGCG可能通过抑制p75NTR介导的JNK/c-Jun/p53凋亡相关信号通路,抑制D-gal诱导AD模型大鼠脑内神经细胞凋亡,从而改善其认知障碍。
引用
收藏
页码:574 / 578
页数:5
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