孕期低水平铅暴露对子代大鼠海马神经生长相关蛋白表达的影响

目的 观察孕鼠低水平铅暴露后子代大鼠海马组织神经生长相关蛋白(GAP-43)及其mRNA表达的变化,探讨铅对学习记忆影响的分子机制.方法 孕鼠随机分为对照组及低(125 mg/L)、中(250 mg/L)、高(500 mg/L)3个不同剂量染铅组,每组8只.各组母鼠自受孕1 d起分别给予蒸馏水、125、250、500 mg/L醋酸铅饮水,直到仔鼠出生.分别在仔鼠出生后1、21,60 d取大脑海马组织,氢化物-原子吸收光谱法测定仔鼠海马铅含量,免疫组化和原位杂交方法检测海马CA1区GAP-43蛋白及其mRNA表达的变化.结果 出生后1、21 d时低、中、高剂量染铅组海马铅含量分别为(1.64±0.32)、(2.33±0.42)、(3.28±0.58)μg/L和(0.94±0.18)、(1.27±0.26)、(1.79±0.42) μg/L,与对照组相比,铅含量明显升高,差异均有统计学意义(P＜0.05).出生后1 d各剂量染铅组和出生后21 d中、高剂量染铅组CA1区GAP-43蛋白和mRNA表达的积分吸光度均明显低于对照组,差异有统计学意义(P＜0.05或P＜0.01),而在60 d时未见明显改变.结论 孕鼠低水平铅暴露后,可以降低子代海马GAP-43蛋白及其mRNA的表达,这可能是铅影响学习记忆的分子机制之一.

Effects of prenatal exposure to low level lead on expression of GAP-43 in hippocampus of rat''s offspring

OBJECTIVE: To observe the effects of prenatal exposure to low level lead on the protein and mRNA expression of growth-associated protein (GAP-43) in hippocampus of rat's offspring, and to explore the molecular mechanisms of lead on learning and memory. METHODS: The pregnant rats were randomizedly divided into 4 groups and provided with doubly evaporated water in control group and 125, 250, 500 mg/L lead acetate solution via drinking water in treatment groups respectively during pregnancy. When the rat's offspring was 1, 21, 60 days old, the lead content in hippocampus was measured by hydride generationatomic absorption spectrometry, and the GFAP protein and mRNA expression at hippocampal CA1 region were observed by immunohistochemistry and in situ hybridization. RESULTS: The content of lead in the hippocampus was (1.64 +/- 0.32), (2.33 +/- 0.42) and (3.28 +/- 0.58) microg/L, and (0.94 +/- 0.18), (1.27 +/- 0.26) and (1.79 +/- 0.42) microg/L respectively in the low, middle and high lead dosage group when the rat's offspring was one day and 21 day old. When the rat's offspring was 1, 21 days old, the content of lead in hippocampus in treatment groups was significant higher than that of control (P < 0.05), the integral optical density of GAP-43 protein and mRNA expression (except low dosage treatment at 21 d) were significantly decreased compared with the control (P < 0.01, P < 0.05), but there was no significant difference at 60-day old offsprings for the parameters above. CONCLUSION: Exposure to low level lead during pregnancy could inhibit the GAP-43 protein and mRNA expression in hippocampus of rat's offspring, which may be one of the molecular mechanisms of lead on learning and memory.