β-淀粉样蛋白对大鼠学习记忆、病理及tau蛋白磷酸化的影响

目的研究大鼠海马区内注射β-淀粉样蛋白（Aβ）的神经毒性,建立阿尔茨海默病（AD）动物模型,探讨Aβ毒性机制。方法选取雌性成年SD大鼠24只,随机分为止常对照组、生理盐水组、AD组,每组8只。Morris水迷宫检测大鼠学习记忆功能,HE染色及B ielschowsk i染色法观察海马神经元形态,免疫组化法观察tau蛋白异常磷酸化变化。结果与正常对照组大鼠相比,AD组大鼠水迷富测试结果明显减退（P〈0.01）;海马CA1区神经元纤维形态紊乱,tau蛋白磷酸化阳性细胞数明显增多（P〈0.01）。结论大鼠海马内注射凝集态Aβ可产生神经毒性作用,能较好地模拟AD行为和病理表现,其神经毒性可能是通过tau蛋白的异常磷酸化起作用。

The influence of beta-amyloid on learning and memory,histologic changes and tau hyperphosphorylation in rats

Objective To explore the neurotoxicity mechanism of beta-amyloid（Aβ） by establishment of Alzheimer＇s disease model with injection Aβ to hippocampus in rats.Methods 24 female rats were divided into three groups randomly： normal control group,saline group and AD group with each group 8 rats.The function of learning-memory was tested by Morris water maze.The pathological changes of hippocampus neurons were observed by both H-E staining and Bielschowski staining.The tau hyperphosphorylation was detected by immunohistochemistry staining.Results Compared with the normal control group rats,the function of learning-memory in AD group was impaired significantly（P0.01）,the neurofibrils in hippocampus neurons were disordered,and the number of P-tau positive cells was remarkably increased （P0.01）.Conclusion The injection of aggregated Aβ25-35 to rat hippocampus can produce neurotoxicity,which mimics the performance of AD and pathological characterizations exactly.The tau hyperphosphorylation may be involved in the neurotoxic mechanisms of Aβ.