摘要
目的探讨丝裂酶原激活蛋白激酶(mitogen activated protein kinase,MAPK)在阿尔茨海默病(Alzheimer's diease,AD)发病中的变化及其可能机制.方法 将β-淀粉样肽(beta-amyloid peptide,Aβ)1～40 1μl(10 μg/μl)在立体定位仪下注入大鼠海马建立大鼠AD模型,2周后测长时程增强(long term potentiation,LTP)、免疫组化SABC法检测MAPK的蛋白表达.结果 AD模型组Aβ注射2周后,模型组刺激前后fEPSP斜率变化及高频刺激增加的幅值与对照组相比显著下降(P＜0.01);模型组海马CA1区、CA2区磷酸化的MAPK蛋白的表达显著低于正常对照组(P＜0.05或P＜0.01).结论 Aβ可能通过抑制MAPK信号通路,导致大鼠海马LTP降低,参与AD学习记忆障碍和痴呆形成.
Objective To investigate the change of mitogen activated protein kinase（MAPK） in the hippocampus of Alzheimer disease（AD） rat model. Methods AD rat model was established by injection of amyloid-beta protein（ Aβ, 1 - 40 μl,10μg/μl） into hippocampus of rat. Long term potentiation（LTP） was determined by electrophysiological method. Phosphorylated MAPK protein was immunostained by immunohistochemistry method. Resuits Two weeks after injection of Aβ ,the slope alteration of field-excitory postsynaptic potentiation（fEPSP） between pre- and post-high-frequency stimulation（HFS） was decreased in Alzheimer rats than in control（ P 〈0.01 ）. The augmented amplitude of fEPSP by HFS was lower in Alzheimer rats than in control. Phosphorylated MAPK immunoreacfive positive neurons in CA1 and CA2 areas of hippocampus were remarkably downexpressed in Alzheimer rats than in control rats. Conclusion Aβ causes the decrease of LTP by inhibiting MAPK signal pathway, and MAPK may be involved in the pathogenesis of Alzheimer disease.
出处
《解剖科学进展》
CAS
2005年第3期222-224,227,共4页
Progress of Anatomical Sciences
基金
国家自然科学基金资助项目(No.30400145No.30070268)
