Exendin-4对淀粉样β蛋白所致大鼠学习记忆和海马神经元胞内钙离子的影响

摘要

目的 探讨Exendin-4对淀粉样 β 蛋白( Aβ1-42)所致大鼠学习记忆及对大鼠海马神经元细胞内钙离子浓度的影响.方法 SD雄性大鼠( n= 40)分为对照组、Aβ1-42、Exendin-4、Exendin-4 + Aβ1-42等4组.双侧海马注射 Aβ1-42 建立阿尔茨海默病(AD)模型,Exendin-4预处理后进行Morris水迷宫实验检测大鼠的学习记忆能力, 利用激光扫描共聚焦显微成像技术检测海马神经元细胞内钙离子[Ca2+]i荧光强度.结果 与对照组相比, 海马单独注射 Aβ1-42 可导致大鼠学习记忆能力明显下降( P<0.05);单独注射Exendin-4不影响大鼠的学习记忆, 但Exendin-4预处理可有效逆转 Aβ1-42 引起的学习记忆损伤(P>0.05);Exendin-4预处理逆转了Aβ1-42引发的海马神经元细胞内Ca2+的浓度增高(P<0.05).结论 Exendin-4可有效拮抗 Aβ1-42 所致的大鼠空间学习记忆伤害,作用机制可能通过调节AD模型大鼠海马神经元细胞内钙离子稳态.%Objective To explore the effects of exendin-4 on amyloid β-protein (Aβ) 1-42-induced deficits in learning memory and intracellular calcium concentration of hippocampal neuron in rats.Methods Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n=10,each group):control, Aβ1-42 , Exendin-4, Exendin-4+Aβ1-42.After bilateral hippocampal injection of Aβ1-42 and exendin-4 rats,Morris water maze test was used to test the ability of spatial learning and memory,and laser-scanning confocal calcium imaging technique was used to test the [Ca2+]i in primary cultured rat hippocampal neurons.Results Hippocampal injection of Aβ1-42 alone impaired spatial learning and memory of rats (P<0.05).Exendin-4 did not affect learning and memory of rats,but alleviated Aβ1-42-induced spatial learning and memory deficits,compared with Aβ1-42 alone group (P>0.05).Pretreatment with exendin-4 suppressed Aβ1-42-induced elevate on in intracellular calcium concentration [Ca2+]i.(P<0.05).Conclusion These findings indicate that systemic pretreatment with exendin-4 can effectively prevent the impairment in spatial learning and memory of rats induced by neurotoxic Aβ1-42, and the underlying protective mechanism of exendin-4 may be involved in regulation of calcium homeostasis.