慢性铅暴露对大鼠GAP-43蛋白表达和学习记忆影响

Impact of chronic low-level lead exposure on neuronal growth associated protein expression of hippocampus and learning-memory in rats

目的探讨发育期慢性低浓度铅暴露对大鼠学习记忆及脑海马神经生长相关蛋白(GAP-43)表达影响。方法 30只孕鼠随机分为3组,自受孕1 d起,分别给予蒸馏水,0.05%,0.2%醋酸铅饮水,断乳后仔鼠自行饮用含铅水,至出生后28 d;生后56 d用水迷宫方法测试仔鼠学习记忆行为改变;蛋白印迹实验(Western blot)方法检测脑海马GAP-43蛋白表达。结果发育期慢性低浓度铅暴露可致大鼠空间学习记忆能力下降,与对照组比较,差异有统计学意义(P<0.05);生后1、3、7、14、21、28 d,0.05%,0.2%醋酸铅组脑海马GAP-43表达量分别为(0.258±0.089)、(0.832±0.021)、(0.806±0.047)、(0.933±0.010)、(0.593±0.004)、(0.437±0.015)和(0.115±0.010)、(0.590±0.018)、(0.680±0.027)、(0.703±0.004)、(0.450±0.014)、(0.325±0.007),均明显低于对照组(P<0.05)。结论铅致仔鼠空间学习能力下降,与脑海马GAP-43蛋白表达水平下降有关。

Objective To explore the effect of chronic low-level lead exposure at developmental stages on learning-memory and the expression of neuronal growth associated protein 43（GAP-43） in hippocampus in rats.Methods Thirty pregnant rats were randomly divided into 3 groups and provided with distilled water in control group and 0.05%,0.2% lead acetate solution via drinking water in treatment groups.During pre-weaning the offspring of lead-exposed group drank lead acetate through breast milk,and they continued to drink the same concentration of lead acetate after weaning until 28th day after the birth（PN28）.Morris water maze was applied to observe the special learning and memory of the rats of PN28.Western blot technique was applied to detect the change of expression of GAP-43 in hippocampus.Results The scores of Morris water maze task were significantly reduced in Pb-exposed groups compared with that of the control group（P 0.05）.In the hippocampus,the protein expression in Pb-exposed group（0.05%PbAc：0.258±0.089,0.832±0.021,0.806±0.047,0.933±0.010,0.593±0.004,0.437±0.015;0.2%PbAc：0.115±0.010,0.590±0.018,0.680±0.027,0.703±0.004,0.450±0.014,0.325±0.007） exhibited a significant decline at the time of 1,3,7,14,21,and 28 days after the birth compared to those of the control group（P0.05 for all）.Conclusion Chronic lead exposure results in decrease of special learning and memory and its effect may related to the decline of expression of GAP-43 in hippocampus.