孕哺期铝暴露对仔鼠海马 N-甲基-D-天门冬氨酸受体表达的影响

目的 研究孕哺期染铝对仔鼠学习记忆和仔鼠海马组织中N-甲基-D-天门冬氨酸受体(NMDAR)表达的影响,以探讨铝对发育中的中枢神经系统的毒性作用及机制.方法 Wistar大鼠60只,雌雄各半,饲养1周后按1∶1雌雄合笼,发现阴栓即可认为雌鼠怀孕,按体重将孕鼠随机分为3组:对照组(饮用蒸馏水)、低剂量组(饮用0.2%AlCl3蒸馏水溶液)、高剂量组(饮用0.4%AlCl3蒸馏水溶液),每组10只,母鼠从怀孕开始染毒,至仔鼠哺乳期(出生后21 d)结束,共染毒6周.原子吸收石墨炉法测 定血铝和脑铝含量;跳台试验法观察大鼠学习、记忆行为学的改变;用免疫印迹(Western blot)法测定海马NMDA受体表达水平.结果 随着染铝剂量的增加,仔鼠血铝、脑铝含量明显增加,与对照组比较,差异有统计学意义(P＜0.05).低、高剂量染铝组仔鼠跳台试验的潜伏期逐渐缩短[分别为(202.71±81.99)、(19.67±8.44)s],与对照组[(300.00±0.00)s]比较,差异有统计学意义(P＜0.01),而错误次数逐渐增加(低、高剂量染铝组分别为1.43±0.85、2.47±0.99),与对照组(0.00±0.00)比较,差异有统计学意义(P＜0.01).铝暴露也可导致NMDAR各亚型的比例发生变化,低、高剂量染铝组仔鼠海马组织中NR1和NR2B含量下降(低剂量染铝组NR1和NR2B灰度值为25.22±0.68、81.23±15.37,高剂量染铝组NR1和NR2B灰度值为24.75±0.71、56.63±7.82,与对照组(NR1和NR2B灰度值分别为31.69±3.44、107.61±9.05)比较,差异均有统计学意义(P＜0.05).结论 孕哺期铝暴露可以引起发育中大鼠学习记忆能力下降,导致NMDAR各亚型的比例发生变化,NR1和NR2B含量下降可能是母体铝暴露影响子代大鼠学习记忆能力的重要分子机制之一.

Abstract：

Objective To investigate the effects of aluminum on learning and memory and the expression of N-methyl-D-aspartic acid receptor (NMDAR) of hippocampus in offspring from female rats exposed to Al in the pregnancy or lactation, and to explore the mechanism of toxic effects of Al on central nervous system (CNS) during development. Methods The pregnant Wistar rats were randomly divided into 3 groups based on their body weight, I.e. Control group was exposed to distilled water, low exposure group (0.2 %AlCl3) and high exposure group (0.4 %AlCl3) were exposed orally to AlCl3 in pregnancy and lactation for 6 weeks, 10 rats each group. Aluminum content in blood and brains was determined by atomic absorption spectrophotometry (AAS). Platform experiment was used to detect the abilities of learning and memory. The expression levels of NMDARs were detected by western blot assay. Results The Al content in blood and brains of rats in exposure groups increased significantly with Al dose, as compared with the control group ( P＜0.05 ). In platform experiment, the incubation periods of rats in low and high exposure groups were (202.71±81.99 ) and ( 19.67±8.44 )s respectively, which were significantly lower than that [( 300.00±0.00 )s] in control group (P＜0.01), but the mistake times of rats in low and high exposure groups were 1.43±0.85 and 2.47±0.99 respectively, which were significantly higher than that (0.00±0.00) in control group (P＜0.01). The Al exposure could change the proportion of NMDAR subtypes, the expression levels of NR1 and NR2B in hippocampus of newborn rats in low and high exposure groups were 25.22±0.68, 81.23±15.37 and 24.75±0.71, 56.63 ±7.82, respectively, which were significantly lower than those (31.69±3.44, 107.61±9.05 ) in control group (P＜0.05). Conclusion Aluminum exposure in pregnancy and lactation could reduce theabilities of learning and memory in newborn rats, and change the proportion of NMDAR subtypes. The reduced NR1and NR2B expression levels may be one of important mechanisms to influence the abilities of learning and memory in offspring.

The expression changes of N-methyl-D-aspartic acid receptor in hippocampus of offspring from female rats exposed to aluminum in the pregnancy and lactation

Objective To investigate the effects of aluminum on learning and memory and the expression of N-methyl-D-aspartic acid receptor (NMDAR) of hippocampus in offspring from female rats exposed to Al in the pregnancy or lactation, and to explore the mechanism of toxic effects of Al on central nervous system (CNS) during development. Methods The pregnant Wistar rats were randomly divided into 3 groups based on their body weight, I.e. Control group was exposed to distilled water, low exposure group (0.2 %AlCl3) and high exposure group (0.4 %AlCl3) were exposed orally to AlCl3 in pregnancy and lactation for 6 weeks, 10 rats each group. Aluminum content in blood and brains was determined by atomic absorption spectrophotometry (AAS). Platform experiment was used to detect the abilities of learning and memory. The expression levels of NMDARs were detected by western blot assay. Results The Al content in blood and brains of rats in exposure groups increased significantly with Al dose, as compared with the control group ( P＜0.05 ). In platform experiment, the incubation periods of rats in low and high exposure groups were (202.71±81.99 ) and ( 19.67±8.44 )s respectively, which were significantly lower than that [( 300.00±0.00 )s] in control group (P＜0.01), but the mistake times of rats in low and high exposure groups were 1.43±0.85 and 2.47±0.99 respectively, which were significantly higher than that (0.00±0.00) in control group (P＜0.01). The Al exposure could change the proportion of NMDAR subtypes, the expression levels of NR1 and NR2B in hippocampus of newborn rats in low and high exposure groups were 25.22±0.68, 81.23±15.37 and 24.75±0.71, 56.63 ±7.82, respectively, which were significantly lower than those (31.69±3.44, 107.61±9.05 ) in control group (P＜0.05). Conclusion Aluminum exposure in pregnancy and lactation could reduce theabilities of learning and memory in newborn rats, and change the proportion of NMDAR subtypes. The reduced NR1and NR2B expression levels may be one of important mechanisms to influence the abilities of learning and memory in offspring.