p38MAPK在Aβ_(25-35)诱导AD大鼠海马CA1区表达的研究

Expression of p38MAPK in the hippocampal CA1 region of rats with Aβ_(25-35)-induced Alzheimer disease

目的探讨p38MAPK在AD大鼠发病中的变化及其可能机制。方法采用Aβ25-35单次侧脑室注射诱导AD大鼠模型,Y迷宫实验测定大鼠行为学变化,免疫组化法检测建模后4、7和14d时痴呆组、生理盐水组、抑制剂组和抑制剂对照组大鼠海马CA1区磷酸化p38MAPK的表达。结果Aβ注射7、14d后,痴呆组的大鼠达到学习标准的训练次数(N)、错误次数(EN)和全天总反应时间(TRT)较生理盐水组均明显增加(P<0.05);抑制剂组N,EN,TRT均比痴呆组明显减低(P<0.05)。免疫组化结果:痴呆组Aβ注射4d起,海马CA1区磷酸化p38MAPK表达即增高(P<0.01),且随着观察时点的延长,这种表达进一步增高(P<0.01);抑制剂组p38MAPK的表达比痴呆组明显减低(P<0.01)。结论大鼠侧脑室注射Aβ7d可成功诱导AD大鼠模型;p38MAPK的激活贯穿Aβ诱导AD大鼠模型的全过程;SB203580可抑制p38MAPK的表达,改善痴呆大鼠的学习记忆能力。

Objective To investigate the changes of p38MAPK expression in a rat model of Alzheimer disease （AD）. Methods Seventy-two adult SD rats were randomized equally into 4 groups, and a single-dose injection of Aβ25-35 （dementia group）, normal saline （saline group）, SB203580 （inhibitor group）, or DMSO （inhibitor control group） was administered into the lateral cerebral ventricle. Y-maze tast was performed to evaluate the behavioral changes of the rats after the injections, and on days 4, 7 and 14 after the injection, p38MAPK expression in the hippocampal CA1 area was measured by means of immunohistochemistry. Results On days 7 and 14 following Aβ25-35 injection, the training times, error number and total reaction time were significantly higher in dementia group than in saline group （P〈0.05）, but all these indices were significantly lowered in the inhibitor group as compared with the dementia group （P〈0.05）. Immunohistochemistry revealed obvious p38 expression in the dementia group 4 days after Aβ25-35 injection, which increased significantly with the passage of time （P〈0.01）. The gray scale in the inhibitor group was significantly higher than that in the dementia group （P〈0.01）. Conclusion p38MAPK activation in the hippocampal CA1 area is an event that persists during the entire course of Aβ25-35;induced AD in rats, and the inhibitor SB203580 prevents p38MAPK expression and improves the learning and memory abilities of the rats.