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。
Objective To investigate the anti-AD effects on the cognitive performance and to reveal the related mechanism on p75NTR-mediated apoptosis signaling in D-gal-induced AD model rats after EGCG treatment. Methods Morris water maze（ MWM）was used for evaluating the cognitive performance,the neuronal apoptosis was detected by both TUNEL staining and Cleaved-Caspase-3expression level. Western blotting was applied to determine the expression levels of p75NTR-mediated apoptosis signaling.Results EGCG treatment significantly ameliorated the cognitive impairments,dramatically reduced the staining levels of TUNEL-positive cell and decreased the apoptosis marker Cleaved-Caspase-3 expression. Futhremore,EGCG inhibited p75 NTR signaling by decreasing the expression level of p75 ICD,following by reducing the phosphorylation of JNK2 and c-Jun,and droping the p53 expression in the D-gal-induced AD model rats. Conclusion EGCG treatment can improve the cognitive impairments in the D-gal-induced AD model rats by inhibiting neuronal apoptosis mediated by p75 NTR signaling.
出处
《临床军医杂志》
CAS
2016年第6期574-578,共5页
Clinical Journal of Medical Officers
基金
国家科技部"重大新药创制"科技重大专项子课题(2013ZX09103001-003)
国家自然科学基金资助项目(81501098)
辽宁省科学技术计划项目(2013225079)
