阿魏酸钠对抗Aβ(25-35)致大鼠学习记忆障碍与IL-1β和p38MAPK表达的相关性探讨

Effects of sodium ferulate on Aβ_(25-35)-induced cognitive deficits and expression of IL-1β and p38MAPK in rats

目的研究阿魏酸钠(sod ium feru late)对抗Aβ25-35致大鼠学习记忆障碍与白介素-1β(IL-1β)和丝裂原激活的蛋白激酶p38(M itogen-activated prote in k inase,p38MAPK)表达的相关性。方法大鼠脑室内一次性注射Aβ25-35制备AD动物模型,通过大鼠行为学和海马CA1区的病理学改变观察阿魏酸钠的作用。W estern b lot和ELISA方法检测磷酸化p38MAPK和IL-1β蛋白表达量的变化。RT-PCR分析FasLmRNA表达水平。结果脑室内注射Aβ25-35可使大鼠出现明显的学习记忆障碍,即逃避潜伏期明显延长,原平台象限游泳时间占总游泳时间百分比明显降低。这些行为学的改变伴随有海马CA1区星形胶质细胞激活和浸润,IL-1β蛋白表达和FasL mRNA表达水平明显增加,海马CA1区锥体神经元损伤。另外,Aβ25-35也能引起磷酸化的p38MAPK蛋白表达明显增加。阿魏酸钠(50,100,250 mg.kg-1,连续应用4 wk)与阳性对照药布洛芬(15 mg.kg-1)均能明显对抗Aβ25-35所致大鼠学习记忆障碍,抑制Aβ25-35引起的IL-1β、磷酸化p38MAPK和FasL mRNA表达增加,海马CA1区锥体神经元的损伤和星形胶质细胞激活和浸润也被明显减轻。结论阿魏酸钠通过抑制Aβ25-35引起的海马炎症反应和p38MAPK活性,减轻大鼠海马锥体神经元的损伤,改善大鼠的学习记忆功能。

Aim To study the effects of sodium ferulate on Aβ-induced cognitive deficits and expressions of IL- 1β and phospho-p38MAPK proteins. Methods Alzheimers disease model of rats was produced by intracerebroventricular injection of Aβ25.35 （10 μg, once）. Morris water maze was used to measure spatial memory performance. Nissl staining and immunohistochemical technique for glial fibrillary acidic protein （GFAP） were employed to determine the morphology of pyramidal neurons and astrocyte infiltration in hippocmpal CA1 regions. The levels of phospho-p38MAPK and IL-1 β were determined by Western blot and ELISA method. Reverse transcription-PCR analysis showed changes in FasL mRNA. Results Intracerebroventricular injection of Aβ25-35in rats resulted in spatial memory impairments shown by longer sulted escape latency and decreased percentage of time spent in the target quadrant. These behavioral dysfunctions were accompanied by astrocyte activation and infiltration, increased IL-1β production and elevated FasL mRNA level, the loss of pyramidal neurons in hippocampal CA1, and the increase of phosphorylated p38MAPK. Oral administration of sodium ferulate （50, 100, 250 mg ·kg^-1 daily） and ibuprofen 15 mg ·kg^-1 daily markedly improved the memory impairment, attenuated pyramidal neuronal damage ses in IL-1β and sodium ferulate , and reversed the Aβ-induced increa p38MAPK activation. Conclusion prevents Aβ-induced neurotoxicity through suppressions of inflammatory response and the activation of p38MAPK.