慢性铝暴露对大鼠海马钙离子稳态及CaMK Ⅱ和CREB活性的影响

Effect of chronic aluminum exposure on calcium homeostasis and activities of Ca MKⅡ and CREB in hippocampus of rats

目的通过研究慢性铝暴露对大鼠海马钙离子稳态及Ca MKⅡ和CREB活性的影响,探讨慢性铝暴露诱导神经损伤可能存在的机制。方法选用60只断乳后雄性Wistar大鼠,分为3组,每组20只;设定其中1组为对照组,用蒸馏水喂养;其他2组为铝暴露组,分别用含有0.2%和0.4%Al Cl3的蒸馏水喂养3个月。Morris水迷宫测定各组大鼠学习记忆能力;Fura-2/AM测定各组大鼠海马神经细胞自由Ca2+浓度变化;Western印迹方法检测各组大鼠海马中Ca MKⅡ、Ng和CREB的蛋白表达情况。结果大鼠的学习记忆能力明显降低;与对照组相比,铝暴露各组海马神经细胞中〔Ca2+〕i呈剂量依赖性升高;Ca MKⅡ和CREB总蛋白表达无显著变化,但p-Ca MKⅡ、Ng和p-CREB蛋白表达显著降低(P<0.05)。结论慢性铝暴露损伤大鼠的学习记忆可能与上调Ca2+及抑制Ca MKⅡ和CREB活性相关。

Objective To study the potential mechanism of aluminum-induced memory injury through the research on effect of chro-nic aluminum exposure on calcium homeostasis and activities of CaMKⅡand CREB in hippocampus of rats.Methods 60 weaning rats were divided into 3 groups, which were given distilled water containing 0.2% AlCl3 and 0.4% AlCl3 respectively for 3 months to establish the chronic aluminum exposure model.Morris water maze was used to evaluate the learning and memory ability;the freedom Ca2+in hippocampal neurons of rats was measured with Fura-2/AM;Western blot was used to determine the expressions of CaMKⅡ, Ng and CREB.Results Learning and memory abilities of rats were significantly reduced;the expressions of p-CaMKⅡ, Ng and p-CREB in the hippocampus of alu-minum-treated groups were significantly lower than those in control group(P<0.05), but there were no changes in the expressions of total CaMKⅡand CREB;and the aluminum-treated groups had the higher Ca2+level than that of control group(P<0.05).Conclusions Chronic aluminum exposure could impair the ability of learning and memory of rats, which is closely related to the up-regulation of Ca2+level and the down-regulation of CaMKⅡand CREB activities.