Aβ_(1-42)注射后大鼠海马神经元凋亡及线粒体凋亡途径相关蛋白表达变化的研究

Study on Apoptosis of Neurons in Rat Hippocampus and Expression of Related Proteins in Path of Mitochondrion after Injection of Aβ_(1-42)

目的:研究大鼠海马注射淀粉样β蛋白(β-amyloid,Aβ)后海马神经元凋亡及线粒体凋亡途径相关蛋白表达的变化,探讨其在阿尔茨海默病发病机制与病理改变中的作用。方法:SD大鼠36只随机分为正常对照组,生理盐水组和模型组。大鼠双侧海马注射Aβ_(1-42)建立AD模型,不同时间点Y迷宫进行行为学测试,TUNEL法检测海马神经元凋亡表达,western-blot检测海马细胞色素C、caspase-9蛋白表达。结果:模型组大鼠术后14天达到学会标准所需电击次数较生理盐水组和正常对照组增加(P<0.05),21天、28天增加更显著(P<0.01)。模型组凋亡细胞数较正常对照组、生理盐水组明显增多(P<0.01)。模型组大鼠海马细胞色素C与caspase-9蛋白表达明显高于生理盐水组与正常对照组(P<0.05)。结论:Aβ_(1-42)海马注射通过激活线粒体凋亡途径诱导海马神经元凋亡.引起大鼠学习记忆能力损害,在AD的发病机制与病理进程中发挥重要作用。

＇Objective： To study the neuron apoptosis and the changes of the proteins related to mitochondrial pathways of apoptosis expression in hippocampus of Alzheimer disease （AD） model rats and discuss these results＇ significance in the pathogenesy and pathology of AD. Methods： 36 SD rats were divided into normal group, saline group and model group. The AD model rats were established by injection β-amyloid 1-42 （Aβ1-42） into hippocampus. Learning and memory ability was estimated with Y maze at different time. The apoptotic neurons were detected by TUNEL method. Cytochrome C and caspase-9 protein expression in hippocampus were detected by Western-blot. Results： The frequency of attempting learning and memory of rats in model group was increased more than the rats in normal group and saline group significantly （P〈0.05） at the 14th day after injection. And at the 21st and 28th day after injection, the difference was more remarkably （P〈0.01）. The apoptotic neurons in hippocampus of the rats in model group were increased more significantly than that in normal group and saline group （P〈0.01）. The expressions ofcytochrome C and caspase-9 in hippocampus of the rats in model group were increased significantly compared with normal group and saline group （P〈0.05）. Conclusions： Aβ1-42 injection in hippocarnpus of the rats can induce the apoptosis of hippocampal neurons through activating mitochondrial pathways of apoptosis and result in the impairment of the learning and memory ability of rats. And it plays an important role in the pathogenesy and pathology of AD.