双侧内嗅皮质注射β淀粉样蛋白对大鼠学习记忆能力的影响及局部病理改变  

Bilateral injection of Aβ into entorhinal cortex of rats induces cognitive deficits and local pathology

作　　者：刘春喜[1] 黄耀德[2] 刘文超[2] 李志宏[2] 

机构地区：[1]山东大学齐鲁医院教育部、卫生部心血管重构和功能研究重点实验室,济南250012 [2]上海交通大学基础医学院解剖学教研室

出　　处：《中国行为医学科学》2008年第7期594-596,共3页Chinese Journal of Behavioral Medical Science

摘　　要：目的观察β淀粉样蛋白（Aβ）的在体神经毒作用及其对大鼠学习记忆能力的影响。方法将聚集态Aβ微量注射于大鼠双侧内嗅皮质（EC），对照组注射生理盐水（NS），术后第7，8天采用Y-迷宫进行行为学测试，测试后处死动物取材，分别采用尼氏染色、HE染色、刚果红染色观察EC的病理改变。结果NS组大鼠获得记忆和再现记忆累积尝试次数分别是（19．17±5．58）次、（10．56±1．72）次，Aβ组大鼠获得记忆和再现记忆尝试次数分别是（31．13±6．98）次、（18．47±4．64）次，组间差异有显著性（P〈0．01）；Aβ组注射区刚果红染色阳性，并有Aβ沉积、神经元丢失、胶质细胞增生，受损面积明显大于NS组，受损面积与动物的学习记忆水平呈现出负相关性（r=-0．241，P〈0．05）。结论双侧EC注射聚集态Aβ可以引起动物学习记忆障碍，注射区局部的病理改变与阿尔茨海默病（AD）典型的老年斑（SP）相似，说明聚集态Aβ具有明确的神经毒作用，EC内注射Aβ有望成为研究AD发病机理与Aβ相关药物筛选的动物模型之一。Objective To investigate the neurotoxicity of β-amyloid protein （Aβ） in vivo and its effects on rats＇ learning and memory ability. Methods The aggregated Aβ （25-35） was injected bilaterally into entorhinal cortex（EC） of rats. Control rats were injected with saline water. All rats were subjected to Y-maze task at 7 d and 8d after operation. After behavioral testing, the rats were sacrificed. The neurpathological changes of EC were examined by Nissl staining, HE staining and Congo Red staining. Results The cumulative number of electric shocks in acquisition test and retention test of the saline group was 19.17 ±5.58 and 10.56 ± 1.72 31 respectively. The corresponding number in Aβ-treated rats was 31.13 ± 6.98 and 18.47 ± 4.64, and significantly increased compared with control group （ P〈0.05 ）. A Congo Red-positive deposit of aggregated material was found at Aβ injection site accompanied by neurons loss and gliacyte reaction. The damaged area of Aβ-treated rats was significantly greater than that of control rats and was negatively correlated with the learning ability （ r = - 0.241, P 〈 0.05）. Conclusion Bilateral injection of aggregated Aβ into EC induces behavioral deficits and amyloid pathology similar to those observed in early phases of AD. These results show definite neurotoxicity of Aβ in vivo. Therefore, injection of Aβ into EC constitutes a promising animal model for investigating selective aspects of AD and for screening drug candidates designed against Aβ pathology.

关 键 词：阿尔茨海默病 内嗅皮质 Β淀粉样蛋白 学习记忆 

分 类 号：R749.16[医药卫生—神经病学与精神病学]