β-淀粉样肽1-40致阿尔茨海默病大鼠模型N-甲基-D-天冬氨酸受体及亚型表达分析

关键词：N-甲基-D-天冬氨酸受体  阿尔茨海默病大鼠模型  Morris 水迷宫  免疫荧光  Western 印迹

Keywords:N-methyl-D-aspartate  Alzheimer′s disease model rat  Morris water maze  immunofluorescence histochemistry  Western blotting

摘要：

      摘要 目的：研究β-淀粉样肽1-40（Aβ1-40）致阿尔茨海默病（AD）大鼠模型前额叶N-甲基-D-天冬氨酸（NMDA）受体及亚型表达与学习记忆之间的关系。 方法：SD大鼠对照组和实验组各12只，分别脑室内注射磷酸盐缓冲液（PBS）和Aβ1-40各10μl。Morris水迷宫检测其学习记忆能力，免疫荧光组织化学检测各组大脑前额叶内NMDA-NR1、NMDA-NR2B分布，Western印迹检测各组大脑前额叶内NMDA-NR1、NMDA-NR2B蛋白表达含量。 结果：实验组参考记忆和工作记忆潜伏期明显低于正常组，大脑前额叶内NMDA-NR1、NMDA-NR2B免疫荧光表达量较弱，大脑前额叶内NMDA-NR1、NMDA-NR2B蛋白表达含量实验组低于正常组，其中NMDA-NR1差异明显（P<0.05）。 结论：Aβ1-40诱导的AD大鼠模型学习记忆功能降低，特别是工作记忆能力明显减弱，与大脑前额叶内NMDA受体表达降低有关，从而部分揭示了前额叶中NMDA受体在学习记忆功能中可能的参与作用。

Abstract:

      Abstract Objective: To analysis the relationship between abilities of learning and memory and expressions of N-methyl-D-aspartate(NMDA)/subunits in prefrontal lobe in beta-amyloid peptide(Aβ1-40) induced Alzheimer′s disease(AD) model rats. Method: Aβ1-40 and phosphate buffered saline(PBS) were infused intracerebroventricularly in 24 Sprague Dawley rats, respectively. Morris water maze was employed to measure rats learning and memory abilities. The distributions and expressions of NMDA-NR1 and NMDA-NR2B in prefrontal lobe were tested by immunofluorescence histochemistry and Western blotting, respectively. Result: The latency of reference memory decreased in two groups, but the decrease trend of AD model rats was slower than that of PBS-infused control rats(P<0.05). The latency of working memory delayed in AD model rats compared with control rats(P<0.05). The expression of NMDA-NR1 in prefrontal lobe was significantly lower in AD model rats than that in control rats(P<0.01). And the expression of NMDA-NR2B in prefrontal lobe was lower in AD model rats than that in control rats, but there was no statistic difference between them. Conclusion: The learning and memory abilities were destroyed in AD model rats by infusion of Aβ1-40 , especially the working memory was destructed markedly. This destruction was related with lower expression of NMDA in the prefrontal. It partly revealed that NMDA in prefrontal lobe might participated the maintenance of learning and memory.