[目的]探讨慢性铝暴露对小鼠学习记忆及tau蛋白磷酸化水平的影响。[方法]将氯化铝(AlCl3)混入饲料中喂养小鼠,分为高、中、低剂量组,剂量分别为120.0、12.0、1.2 mg/(kg.d),对照组正常饲养,每组各10只。染毒期为1年。用Morris水迷宫系统检测小鼠的认知功能,采用电感耦合等离子质谱法测定脑铝含量,免疫印迹法检测小鼠脑组织中总tau蛋白以及tau蛋白在Thr181、Thr231、Ser262和Ser396位点的磷酸化表达。[结果]Morris水迷宫试验,中、高剂量组水迷宫潜伏期高于对照组(P〈0.05),高、中剂量组穿越平台的次数与对照组相比明显减少(P〈0.05)。高、中、低剂量组小鼠脑铝水平明显高于对照组(P〈0.05)。免疫印迹法结果显示,小鼠脑组织总tau蛋白及tau蛋白在Thr181、Thr231、Ser262和Ser396位点的磷酸化表达,高、中、低剂量组明显高于对照组(P〈0.05)。[结论]铝暴露可导致小鼠认知功能障碍及tau蛋白过度磷酸化,这可能是铝致小鼠认知功能障碍的机制之一。
[Objective] To explore the effect of chronic aluminum exposure on learning and memory and the phosphorylation levels of tau protein in mice.[Methods] Three groups of mice were fed with AlCl3 at 120.0,12.0 and 1.2 mg/(kg·d) respectively for 1 year,and one control group with normal diet.Spatial learning and memory ability were tested with Morris water maze(MWM).Brain aluminum content was determined by inductively coupled plasma mass spectrometry(ICP-MS).The expression of total tau and phosphorylated tau in Thr181,Thr231,Ser262 and Ser396 sites in brain tissues of mice were detected by Western blot.[Results] Compared with the control group,the MWM latent period of high and middle dose groups was significantly prolonged(P 0.05);the number of traversing platform in high and middle dose groups were significantly decreased(P 0.05);and brain aluminum levels of all 3 exposure groups were significantly higher(P 0.05).Western blot test demonstrated that the total tau and the phosphorylation levels in Thr181,Thr231,Ser262 and Ser396 sites of all 3 exposure groups were significantly higher than those of the control group(P 0.05).[Conclusion] Aluminum exposure can lead to cognitive dysfunction in mice and the overphosphorylation of tau protein,which may be one of the mechanisms of cognitive dysfunction induced by aluminum.