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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 the effects of low level Pb exposure in pregnant rats on the expression of GDNF in neonatal rats. Methods The pregnant rats were given double distilled water, 0.05%, 0.20% aqueous solution of lead acetate respectively during pregnancy and lactation. The same drinking water was given to the offspring of the female rats after weaning. The rats were sacrificed at 1, 3, 7, 14, 21 , And the changes of GDNF expression in the hippocampus of 28-day-old offspring. The contents of lead and lead in the blood and hippocampus of offspring were measured by graphite furnace atomic absorption spectrometry (GFAAS). The changes of learning and memory in offspring 56 days after birth were observed by water maze test. Results Compared with the control group [(9.01 ± 1.60) s], 0.05% and 0.20% lead acetate groups showed significantly longer (P <0.01) time looking for the plateau [(16.43 ± 2.89) and (24.85 ± 4.44) s] (0.61 ± 0.018), (0.71 ± 0.026), (0.70 ± 0.03), (0.62 ± 0.033), respectively, in the hippocampus of 0.20% lead acetate group 0.74 ± 0.048), (0.86 ± 0.016), (0.97 ± 0.023) and (0.88 ± 0.03), respectively (P <0.05, P <0.01). There was a dose-dependent and time-dependent difference. Conclusion The decreased expression of GDNF in the hippocampus of pregnant rats induced by low level lead exposure may be one of the molecular mechanisms by which lead affects learning and memory.