Aβ1-42寡聚体对大鼠认知功能的影响和神经毒性分析

Impact of Aβ1-42 oligomers on the cognitive function in rats and its neurotoxicity analysis

目的:探讨β淀粉样蛋白42(Aβ1-42)寡聚体对阿尔茨海默病(AD)大鼠认知功能的影响以及其神经毒性的分析.方法:采用Morris水迷宫法筛选出逃避潜伏期少于60 s的60只雄性大鼠随机均分为正常组、PBS对照组、Aβ1-42纤维体组、Aβ1-42寡聚体组.用脑立体定位仪将Aβ1-42寡聚体或纤维体分别注入AD模型鼠的双侧海马,PBS对照组注射等量的PBS,正常组不作任何处理.AD模型建立后第8周,采用Morris水迷宫测试大鼠学习记忆能力的变化,然后在麻醉条件下断头取大脑皮质和海马,冷冻切片,常规H-E染色观察脑组织的病理变化.结果:造模后,与正常组和PBS对照组相比,Aβ1-42寡聚体组和Aβ1-42纤维体组逃避潜伏期较造模前均延长,Aβ1-42寡聚体组大鼠逃避潜伏期长于Aβ1-42纤维体组;Aβ1-42寡聚体可导致大鼠海马和大脑皮质神经元细胞凋亡,镜下可见细胞核固缩,核呈黑紫色,染色质边集,Aβ1-42纤维体对神经元损伤较寡聚体轻.结论:Aβ1-42寡聚体海马内注射可导致大鼠认知功能障碍和神经毒性,且Aβ1-42寡聚体较Aβ1-42纤维体神经毒性要强.Aβ1-42寡聚体导致的认知功能障碍与神经细胞损害有关.

Objective:To explore the impact of Aβ1-42 oligomers on the cognitive function in rats with Alzheimer’s disease（AD）and analyze its neurotoxicity.Methods:Sixty rats with escape latency less than 60 s were randomly selected by using Morris water maze method and were divided into normal group,PBS group,Aβ1-42 fiber group,and Aβ1-42 oligomers group.Aβ1-42oligomers and fiber were injected to the bilateral hippocampus in AD rats;Commensurable PBS was given to the PBS group and nothing was done to the normal group.Eight weeks after model establishment,we used Morris water maze method to check the change of rats’ learning and memory ability.The rats which survived from the Morris water maze at 8 weeks were killed under anethesia.Their cerebral cortex and hippocampus were taken out and made frozen sections to observe pathological characteristics of the brain tissue with HE staining.Results:Compared with normal group and PBS group,the escape latency of rats in Aβ1-42 fiber group and Aβ1-42 oligomers group was extended after testing,which was extended more in Aβ1-42 oligomers group than that in Aβ1-42 fiber group.Aβ1-42 oligomers could lead to neuronal cell apoptosis with purple karyopyknosized nuclei and marginal concentrated chromatin in the hippocampus and cerebral cortex.But Aβ1-42 fiber had less impact on brain neuronal cells than Aβ1-42 oligomers.Conclusion:Aβ1-42 oligomers can lead to cognitive obstruction and neurotoxicity,and it is more toxic than Aβ1-42 fiber.