β淀粉样蛋白膜内片段免疫APP转基因小鼠的脑组织学变化研究

Influence of intramembranous fragment of amyloid-β on APP Tg mice

目的从组织病理学的角度分析不同剂量的淀粉样蛋白膜内片段(intramembranous fragments of amyloid-β,IF-Aβ)对淀粉样前体蛋白(amyloid precursor protein,APP)转基因(transgenic,Tg)小鼠的影响,以确定IF-Aβ疫苗是否对APP Tg小鼠有治疗作用。方法 1)分别用PBS、KLH-IF-Aβ(50μg/只)、KLH-IF-Aβ(100μg/只)和KLH-Aβ42(100μg/只)免疫对照组、IF50组、IF100组和Aβ42组6月龄APP Tg C57BL/6J小鼠,共4次,2.5月;2)ELISA检测血清和脑组织IgG抗体;3)水迷宫检测APP Tg小鼠认知功能变化;4)免疫组化检测模型鼠大脑老年斑的变化;5)HE染色和电镜技术检测小鼠海马组织。结果免疫2.5个月后:1)IF-Aβ疫苗对APP转基因小鼠具有良好的体液免疫原性;2)IF50组小鼠的认知功能加强,大脑皮层区老年斑有所减少,较对照组海马区域组织学有所改善;3)IF100组小鼠的认知功能下降,大脑皮层老年斑明显减少,但组织学观察海马区域损伤加重;4)Aβ42组小鼠认知功能有所提高,大脑皮层老年斑明显减少,组织学观察海马区域损伤有所加重。结论在合适的免疫剂量下,小鼠认知功能的变化和海马区域神经元的损伤情况以及老年斑变化一致;而免疫剂量过大,虽然老年斑减少,但是小鼠的神经组织和细胞损伤加重,认知功能下降。

In this study,the effects of different doses of intramembranous fragments of amyloid-β（IF-Aβ） on amyloid precursor protein（APP） transgenic（Tg） mice were analyzed by pathology-signs observation,to determine appropriate doses of IF-Aβ which would exert therapeutic effects on APP Tg mice.Water maze test indicated that administration of IF-Aβ（50 and 100 μg/mouse respectively） to APP Tg C57BL/6J mice at age of 6 months for 2.5 months could alleviate cognitive impairments which accompanied with decreased Aβ deposition in the brain regions;a histological analysis with immunohistochemistry,HE,and ultrastructural observation suggested that a appropriate immune dose could improve cognitive function and decrease senile plaque of mice;when immune dosage is too large,although the senile plaque decreases,but the neural tissue and cell injury increases and the cognitive function declines in mice.