阿尔茨海默大鼠嗅球p38MAPK的表达

Expression of p38MAPK in the Olfactory Bulb of Rats with Alzheimer's Disease

目的观察阿尔茨海默(AD)大鼠嗅球p38MAPK的表达,探讨p38MAPK在AD病理改变发生中的作用机制。方法采用大鼠侧脑室注射Aβ25-35建立AD动物模型,Y迷宫实验测定行为学变化,免疫组化染色法检测建模后4d、7d和14d时AD组、生理盐水组、抑制剂组和抑制剂对照组p38MAPK在大鼠嗅球中的表达。结果①建模后7d、14dAD组大鼠行为学测试出现明显改变,学会训练次数(N)、完成所有反应中错误反应的次数(EN)及全天总反应时间(TRT)均较生理盐水组增加(P<0.05),抑制剂组较AD组N、EN和TRT均有明显改善。②AD组在建模后4d,嗅球出现明显的p38MAPK表达,且随时间的延长表达增加(P<0.05),与生理盐水组比较,AD组p38MAPK阳性细胞数明显升高(P<0.01)。抑制剂组p38MAPK的表达在3个时间点,较AD组、抑制剂对照组均明显下降(P<0.01)。结论Aβ25-35可激活痴呆大鼠嗅觉中枢p38MAPK信号转导通路,p38MAPK可能参与了AD早期嗅觉障碍的形成过程。p38MAPK抑制剂SB203580能部分减弱Aβ25-35的神经毒性作用。

Objective To identify the changes of expression of p38MAPK in the olfactory bulb （OB） of rats with Alzheimer＇s Disease （AD） and to explore the functional mechanism of p38MAPK in the pathological changes of AD. Methods AD animal model was established by injecting amyloid-beta peptide 25-35 into the lateral cerebral ventricle of rats. The learning and memory abilities of rats were measured by Y-maze experiment. The expressions of p38MAPK in the OBs of rats in the AD group, saline control group, p38MAPK inhibitor group and inhibitor control（con-inhibitor） group were examined by immunohistochemistry. Results （1）The capabilities of learning and memory of the rats were impaired significantly at day 7 and day 14 after the induction of AD. Significant learning and memory differences were found （P〈0.05） between the AD group and the other groups. （2）The expression of p38MAPK in the OBs of rats was found at day 4 after the induction of AD. The expression increased with time. The AD rats had more positive p38MAPK cells than those in the saline controls （P〈0.05）. The expression of phosphop38MAPK in the rats with AD increased significantly （P〈0.01） compared with those in the saline group. The AD rats treated with p38MAPK inhibitor had less expression of phospho-p38MAPK than those in the AD group and the inhibitor control （P（0.01）. Conclusions Aβ25-35 can activate p38MAPK signal transduction pathway, p38MAPK may play a role in the formation of dysosmia in AD. SB203580, a p38MAPK inhibitor, can reduce the neurotoxicity evoked by p38MAPK.