锂对慢性铝暴露大鼠学习记忆功能的影响及其机制

The effect and mechanism of lithium on memory function of chronic aluminum chloride exposure rats

目的探讨锂对慢性铝暴露大鼠学习记忆功能以及脑内淀粉样β蛋白前体(APP)代谢的影响。方法将24只慢性铝暴露大鼠随机分为锂治疗组和非治疗组,每组12只;另取12只非铝暴露大鼠为正常组。锂治疗组给予氯化锂溶液(200 mg·kg^(-1)·d^(-1))灌胃,非治疗组以等量氯化钠溶液灌胃,正常组大鼠不进行干预。6周后 Morris 水迷宫测试,比较三组大鼠的学习记忆功能;分别采用免疫组织化学法和免疫印迹法检测各组大鼠脑组织内淀粉样β蛋白(Aβ)和 APP 含量。结果(1)锂治疗组大鼠定向航行实验潜伏期[(15.4±8.7)s]短于非治疗组[(26.8±11.2)8;F=-3.8,P<0.05],空间搜索中随机式所占比例(11.1%)低于非治疗组(20.7%;P<0.05),站台停留时间[(47±7)s]和穿台次数[(12.6±2.2)次]多于非治疗组[(35±7)8和(7.9±2.6)次;P<0.05];(2)正常组大鼠脑内 APP 的含量(1.0±0.3)低于其他两组[锂治疗组为(1.8±0.4),非治疗组为(1.8±0.5);P<0.01]。非治疗组脑内海马、皮层 AB 反应阳性数目多于其他两组(P<0.01)。结论锂可以改善慢性铝暴露大鼠学习记忆功能,可能是通过抑制β分泌酶裂解途径而影响 APP 的代谢,减少Aβ的产生。

Objective To investigate the effect of lithium on memory function and metabolism of amyloid beta-protein precursor （APP） in chronic aluminum chloride exposure rats. Methods Twenty-four chronic aluminum chloride exposure rats were divided into two groups with 12 in each, one was administered lithium chloride via gastric gavage daily, while the other group with same dose of sodium chloride. Another 12 rats without any intervention were as normal controls. After 6 weeks, the memory was tested with the Morris water maze test, and amyloid beta-protein （Aβ） level measured with immunohistochemistry stain while total APP with Western-blotting method. Results Compared to rats with sodium treatment, the rats with lithium treatment had shorter mean escape latency, and decreased proportion of random method in spatial probe test significantly （ P 〈 0. 05 ）. After taken away the platform, the times of passing through the platform were significantly higher in lithium group and the rats stayed much longer in platform quadrant （ P 〈 0. 05 ） than sodium rats. The brain APP content in normal rats was lower than in both groups with aluminum （P 〈 0. 01 ）. The number of Aβ positive neurons both in hippocampus and cortex showed significant less in lithium group than sodium group （ P 〈 0. 05 ）, with no difference on the APP content between lithium and sodium group （P：0. 730）. Conclusion Lithium may improve memory function of the chronic aluminum chloride exposure rats, which is possibly related to affecting the metabolism of APP by prohibiting the β secretase activity to decrease the Aβ production.