发育期铅暴露对大鼠海马GDNF蛋白表达影响

Effect of lead exposure on protein expression of glial cell line-derived neurotrophic factor in hippocampus of offspring rats at developmental stage

目的观察孕鼠低水平铅暴露对仔鼠海马胶质细胞源性神经营养因子(GDNF)表达的影响。方法母鼠孕哺期分别给予双蒸水,0.05%,0.20%,醋酸铅水溶液,断乳后仔鼠给予与其母鼠相同饮用水;采用蛋白印迹法观察出生后1,3,7,14,21,28 d仔鼠海马GDNF表达变化;石墨炉原子吸收光谱法测定出生后28 d仔鼠血铅、海马铅含量;水迷宫实验观察出生后56 d仔鼠学习记忆能力变化。结果 0.05%及0.20%醋酸铅组仔鼠寻找平台时间[(16.43±2.89),(24.85±4.44)s]与对照组比较[(9.01±1.60)s],明显增加(P<0.01),呈剂量效应关系;0.20%醋酸铅组仔鼠海马1,3,7,28 d GDNF表达分别为(0.61±0.018),(0.71±0.026),(0.70±0.03),(0.62±0.033),与对照组(0.74±0.048),(0.86±0.016),(0.97±0.023),(0.88±0.03)比较呈下降趋势(P<0.05,P<0.01),且存在剂量依赖性和时间表达差异。结论孕鼠低水平铅暴露致仔鼠海马GDNF表达减少可能是铅影响学习记忆的分子机制之一。

Objective To observe effects of low level lead exposure during pregnant on expression of glial cell line-derived neurotrophic factor（GDNF） in hippocampus of offspring rats.Methods The rats were fed with doubly evaporated water in control group and 0.05%,0.2% lead acetate（PbAc） solution in treatment groups via drinking water during pregnancy and lactation.After weaning,the offspring rats were directly fed with drinking water as their dams.Western blotting was used to detect the protein expression of GDNF in hippocampus of offspring rats at postnatal 1,3,7,14,21,and 28 days,respectively.The contents of lead in blood and hippocamous were determined with atomic absorption spectrophotometer at postnatal 28 days.The Morris Water Maze test was used to observe the change of learning and memory at postnatal 56 days.Results Compared to the control（9.01±1.60）,the time of searching for the platform was significantly longer in offspring rats of 0.05% and 0.2% PbAc groups（16.43±2.89,24.85±4.44）in dose-effect manner（P0.01）.The expression of GDNF in hippocampus of 0.2%PbAc group at postnatal 1,3,7,and 28 days were 0.61±0.018,0.71±0.026,0.70±0.030,and 0.62±0.033,which exhibited a decreased tendency（P0.05,P0.01） in dose-dependent manner,and different expression with time.Conclusion Exposure to low level lead during pregnancy can decrease expression of GDNF in hippocampus of offspring rats and might be one of the molecular mechanisms of lead on learning and memory.