CAJ | 학술논문

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.
목적 연구잉포기염려대자서학습기억화자서해마조직중N-갑기-D-천문동안산수체(NMDAR)표체적영향,이탐토려대발육중적중추신경계통적독성작용급궤제.방법 Wistar대서60지,자웅각반,사양1주후안1∶1자웅합롱,발현음전즉가인위자서부잉,안체중장잉서수궤분위3조:대조조(음용증류수)、저제량조(음용0.2%AlCl3증류수용액)、고제량조(음용0.4%AlCl3증류수용액),매조10지,모서종부잉개시염독,지자서포유기(출생후21 d)결속,공염독6주.원자흡수석묵로법측 정혈려화뇌려함량;도태시험법관찰대서학습、기억행위학적개변;용면역인적(Western blot)법측정해마NMDA수체표체수평.결과 수착염려제량적증가,자서혈려、뇌려함량명현증가,여대조조비교,차이유통계학의의(P＜0.05).저、고제량염려조자서도태시험적잠복기축점축단[분별위(202.71±81.99)、(19.67±8.44)s],여대조조[(300.00±0.00)s]비교,차이유통계학의의(P＜0.01),이착오차수축점증가(저、고제량염려조분별위1.43±0.85、2.47±0.99),여대조조(0.00±0.00)비교,차이유통계학의의(P＜0.01).려폭로야가도치NMDAR각아형적비례발생변화,저、고제량염려조자서해마조직중NR1화NR2B함량하강(저제량염려조NR1화NR2B회도치위25.22±0.68、81.23±15.37,고제량염려조NR1화NR2B회도치위24.75±0.71、56.63±7.82,여대조조(NR1화NR2B회도치분별위31.69±3.44、107.61±9.05)비교,차이균유통계학의의(P＜0.05).결론 잉포기려폭로가이인기발육중대서학습기억능력하강,도치NMDAR각아형적비례발생변화,NR1화NR2B함량하강가능시모체려폭로영향자대대서학습기억능력적중요분자궤제지일.
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.