蛋白激酶B在铅致小鼠学习记忆功能障碍中的作用  

Effect of protein kinase B on the learning and memory functions of mice with chronic lead exposure

作　　者：彭博[1] 张朝东[2] 任艳[2] 吴哲[2] 

机构地区：[1]中国医科大学门诊部内科,沈阳110001 [2]中国医科大学附属第一医院神经内科,沈阳110001

出　　处：《中华神经医学杂志》2009年第4期363-366,共4页Chinese Journal of Neuromedicine

基　　金：辽宁省博士启动基金（20051035）

摘　　要：目的探讨蛋白激酶B（PKB）在慢性铅暴露所致小鼠学习记忆功能障碍中的作用。方法新生1d昆明系小鼠通过饮水饲以不同浓度醋酸铅（1．2、2．4、4．8、7．2、9．6mmol／L）制备染铅模型（染铅组），对照组饲以等量自来水。6周后经水迷宫行为方法测定小鼠空间学习记忆功能；石墨炉原子吸收光谱法测定小鼠血铅、脑铅浓度；用Western blot法观察各组小鼠大脑皮层神经元总量PKB（t-PKB）2k磷酸化PKB（p-VKB）的磷酸化水平变化。结果染铅组小鼠寻找平台时间均高于对照组，差异有统计学意义（P〈0．05），慢性铅暴露可明显损伤小鼠的空间学习记忆能力，损伤程度与血铅、脑铅的浓度成正相关（r=0．678，P=0．000；r=0．643，P=0．000）；染铅组小鼠大脑皮层神经元p-PKB磷酸化水平均明显降低，并在一定范围内呈浓度依赖性。p-PKB磷酸化水平与血铅浓度呈负相关（r=-0．820，P=-0．028），与学习记忆能力损伤程度呈负相关（r=-0．671，P=0．000）；铅对小鼠大脑皮层神经元t-PKB的磷酸化水平没有影响。结论慢性铅暴露可导致学习记忆功能下降，这可能与慢性铅暴露小鼠中p-PKB磷酸化水平的改变有关。Objective To assess the effect of protein kinase B （PKB） on the learning and memory functions of mice with chronic lead exposure. Methods Since the first day after birth, 50 Kunming mice were randomized into 5 groups （n=10） and exposed to a 6-week acetic lead exposure at the concentrations of 1.2, 2.4, 4.8, 7.2, and 9.6 mmol/L administered in the drinking water, with another 10 having normal water as the control group. After the 6-week exposure, water maze test was performed to assess the spatial learning and memory abilities of the mice. The total PKB （t-PKB） and phosphorylated PKB （p-PKB） in the cortical brain neurons were determined with Western blotting. Results The mean latency of finding the platform in the lead exposure groups was significantly higher than that in the control group （P〈0.05）, Chronic acetic lead exposure resulted in obviously impaired spatial learning and memory ability in the mice, and the severity of the damage was positively correlated to lead concentrations in the blood and brain tissue （r=0.678, P=-0.000; r=0.643, P=0.000）. Lead exposure caused a significant dose-dependent reduction in p-PKB level in the cortical neurons, and p-PKB level in the cortical neurons was inversely correlated to blood lead concentrations （r=-0.820, P=0.028） and to the spatial learning and memory ability （r=-0.671, P=-0.000）. The level of t-PKB in the cortical brain neurons showed no significant changes in response to lead exposure. Conclusion Chronic acetic lead exposure can impair the learning and memory functions of mice possibly in association with reduced content of p-PKB in the cortical brain neurons.

关 键 词：蛋白激酶B 铅中毒 大脑皮层神经元 

分 类 号：R686[医药卫生—骨科学]