快速衰老小鼠的Klotho表达与β淀粉样肽清除的相关性研究

Study on the relationship between Klotho expression and Aβ clearance in senescence-accelerated mice

目的探讨快速衰老小鼠(SAMP8)中Klotho低表达对β淀粉样肽(Aβ)清除的影响。方法采用Y迷宫和跳台实验评测12月龄SAMP8小鼠和抗衰老系列小鼠(SAMR1)的学习和空间记忆能力;免疫组化检测小鼠脑中Aβ1-42、同种异体移植炎性因子-1(AIF1)、胶质纤维酸性蛋白(GFAP)和Klotho的变化;蛋白免疫印迹法检测低密度脂蛋白受体相关蛋白(LRP-1)、晚期糖基化末端产物(RAGE)的蛋白表达。结果与SAMR1小鼠相比,SAMP8小鼠的学习、记忆功能明显下降,脑内Aβ1-42、AIF1、GFAP和RAGE的表达显著增加,Klotho和LRP-1的表达明显降低。结论 SAMP8小鼠中Klotho表达的降低可能导致LRP-1降低和RAGE增加,从而增加Aβ在脑内沉积。

OBJECTIVE To study the role of decreased Klotho involved in Aβ clearance in senescence-accelerated（SAMP8）mice.METHODS Maze and step-down tests were applied to evaluate the learning skill and spatial memory ability of SAMP8 mice at 12 months old and SAMR1 mice.The expression of Aβ1-42,AIF1,GFAP and Klotho were detected by immunohistochemistry.The levels of LRP-1 and RAGE were determined by Western-blot analysis.RESULTS Compared with SAMR1 mice,SAMP8 mice showed their learning skill and memory ability had declined.Aβ1-42,AIFI,GFAP and RAGE had increased,but the expression of Klotho and LRP-1 had decreased.CONCLUSION The decreasing expression of Klotho in SAMP8 mice may lead to LRP-1 reducationand RAGE promotion,further increasing the Aβ accumulation in brain.