【摘要】 目的　研究血液内较高浓度的可溶性 β 淀粉样蛋白1 40 (Aβ1 40 )对毛细血管内皮细胞和胶质细胞的毒性 ,以探讨其在阿尔茨海默病发病中的作用。方法　成年雄性SD大鼠 90只 ,随机分为注射Aβ1 40 组、注射生理盐水组以及正常大鼠 (非手术 )组 ,每组 30只。采用右侧颈外静脉血管插管并留置的方法 ,通过导管向血管内中每日 2次注射 10 μg的可溶性的Aβ1 40 ,连续 14天后 ,采用免疫组化和免疫印迹 (Westernblot)方法观察星形胶质细胞、小胶质细胞的激活状态以及转糖蛋白 1、转糖蛋白 3表达的改变。结果　注射Aβ1 40 以后 ,毛细血管周围星形胶质细胞的胶质纤维酸性蛋白表达明显增多 ;小胶质细胞呈明显的激活状态 ;Westernblot法检测到脑实质内转糖蛋白 1以及转糖蛋白 3表达明显减少。结论　血管内连续注射Aβ1 40 以后 ,对血 脑屏障的内皮细胞有明显的损害 ,对胶质细胞有明显的激活作用 ,可能与AD发病有关。更多还原

【Abstract】 Objective To examine the histopathologic changes of cerebral microvascular endothelial cells and the glia cells in rats after administration of extrinsic Aβ 1 40 and to observe the effects of Aβ 1 40 on the pathogenesis of Alzheimers disease. Methods Aβ 1 40 (10 μg in distilled water)or normal saline water was intravenously infused into 9 month old male Sprague Dawley rats twice per day for 2 weeks. Activation of astrocytes and microglia, and the expressions of GLUT1 and GLUT3 were determined by immunohistochemistry and Western bot. Results After the injections of Aβ 1 40 , numerous ‘activated’ microglias were seen in the brain of rat, an enhancement of GFAP immunoreactivity was evident aroud the small blood vessels in both neocortex and hippocampus; Western blot analysis revealed that the expressions of GLUT1 and GLUT3 decreased. Conclusions Our results suggest that intravenous infusions of Aβ 1 40 impair the intergrity of blood brain barrier and may have some relation to the pathogenesis of AD.更多还原