糖皮质激素促β-淀粉样蛋白致海马神经元损伤的机制  

GCs enhanced Aβ-induced hippocampal neuronal injury in rats

作　　者：陈华跃[1] 朱芬芳[2] 吴庆四[1] 李卫平[2] 姚余有[1] 

机构地区：[1]安徽医科大学公共卫生学院检验医学系 [2]安徽医科大学基础医学院药理教研室,合肥230032

出　　处：《安徽医科大学学报》2008年第5期488-493,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省高校学术带头人后备人选科学研究资助项目(编号:2005hbz18)

摘　　要：目的探讨糖皮质激素(GCs)促进β-淀粉样蛋白(Aβ)引起海马神经元损伤的机制。方法地塞米松(DEX)和Aβ与胎鼠海马神经细胞共同孵育后,通过LDH释放法检测细胞活力,用激光共聚焦显微镜检测神经元[Ca2+]i的变化,用RT-PCR来检测cdk5、p53在细胞内的表达情况。结果DEX促进Aβ25～35引起海马细胞活力的下降(P<0.05),促进Aβ25～35引起上升的[Ca2+]i的水平(P<0.05),上调Aβ25～35引起的上升的cdk5mRNA的水平(P<0.05),但DEX未能进一步促进Aβ25～35引起的上升的p53mRNA水平(P>0.05)。结论DEX可促进Aβ的海马神经元毒性,DEX可能通过上调[Ca2+]i的水平、上调cdk5mRNA的水平促进Aβ引起海马神经元tau异常磷酸化,导致海马神经元损伤。Objective To study whether DEX enhanced Aβ-induced cell death in hippocampal neurons and its related mechanisms.Methods LDH release rate was measured via LDH kit.[Ca2＋]i,Cyclin-dependent kinase-5（cdk5）mRNA,p53 mRNA were detected by Laser Confocal Microscope（LSCM）and RT-PCR analysis respectively.Results The study revealed that in vitro,pretreatment of hippocampal neurons with DEX increased the damage of hippocampal neurons induced by Aβ25~35（P〈0.05）and the level of [Ca2＋]i induced by Aβ25~35（P〈0.05）and up-regulated the increased level of cdk5 mRNA induced by Aβ25~35（P〈0.05）;while pretreatment of hippocampal neurons with DEX did not promote the increased level of p53 mRNA induced by Aβ25~35（P〉0.05）.Conclusion These results demonstrate that DEX could promote the neurotoxic action of Aβ mediated by further increasing the level of [Ca2＋]i and up-regulating the increased level of cdk5 mRNA which induce hyperphosphorylation of tau.

关 键 词：阿尔茨海默病 地塞米松/副作用 淀粉样Β蛋白 海马/病理学 神经元/病理学 

分 类 号：R745.7[医药卫生—神经病学与精神病学] R916.4[医药卫生—临床医学]