PS1/APP双转基因AD模型小鼠与Aβ_(1-40)海马注射AD模型大鼠的组织病理学比较

Histopathologic comparison between PS1/APP double transgenic mouse model and Aβ_(1-40)-injected rat model of Alzheimer disease

目的对PS1/APP双转基因阿尔茨海默病(alzheimerdisease,AD)模型小鼠进行基因鉴定和组织学分析,探讨其与老化态Aβ1-40单侧海马注射AD模型大鼠之间的组织病理学差异。方法对Tg小鼠和AD大鼠模型应用改进刚果红染色法、Nissl’s染色结合免疫组织化学方法观察脑内Aβ沉积和星形胶质细胞的活化情况。结果①PS1/APP双转基因AD小鼠刚果红染色显示皮质和海马内广泛圆形Aβ沉积,周围绕以胶质细胞带,免疫组化显示GFAP阳性细胞活化呈团块聚集。②AD大鼠刚果红染色显示单侧海马齿回区有Aβ斑块状沉积,Nissl’s染色显示注射针道附近海马锥体层细胞丢失,注射侧海马GFAP阳性细胞增多。结论Aβ1-40单侧海马注射AD模型大鼠尽管可以模拟人类AD疾病的部分特征病理改变,但是不能模拟疾病渐进性的病理学改变。PS1/APP双转基因小鼠能够模拟AD病人脑内的主要病理改变与渐进性过程,是较为理想的实验动物模型,但该模型未发现细胞丢失。

Objective To identify the genetype of the PS1/APP double transgenic mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenic mice models and Aβ1-40-injected rat model of Alzheimer disease. Methods The improved congo red staining, Nissl＇s staining and immunohistochemical staining was used to observe the Aβ deposits, activation of astrocyte respectively. Results The PS1/APP transgenic mouse extensively displayed Aβ deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. The Aβ1-40-intrahippocampal-injected rat model showed the Aβ plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neuron loss was significant in the injection point and pin hole of injection with Nissl＇s staining methods. GFAP-positive cells increased significantly as compared with the uninjured lateral of the hippocampus. Conclusion Although Aβ1-40-injected rat models simulate some characteristic pathological features of human Alzheimer diseases, it would not simulate the progressive degenenration in the brain of AD. The double transgenic PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, while no neuron loss was found in this model.