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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 investigate the effect of Klotho overexpression on amyloid β peptide (Aβ) clearance in fast-aging mice (SAMP8). Methods The learning and spatial memory ability of 12-month-old SAMP8 mice and anti-aging mice (SAMR1) were evaluated by Y-maze and platform-jump test. The expressions of Aβ1-42 and allograft inflammatory cytokines- 1 (AIF1), glial fibrillary acidic protein (GFAP) and Klotho were detected by Western blotting. The protein expression of LRP-1 and RAGE was detected by Western blot. Results Compared with SAMR1 mice, the learning and memory abilities of SAMP8 mice were significantly decreased. The expressions of Aβ1-42, AIF1, GFAP and RAGE in brain were significantly increased and the expressions of Klotho and LRP-1 were significantly decreased. Conclusions The decrease of Klotho expression in SAMP8 mice may result in the decrease of LRP-1 and the increase of RAGE, and thus increase the deposition of Aβ in the brain.