【摘要】 目的探讨铅染毒对大鼠空间学习记忆损害的机制。方法将刚出生1天的Wistar仔鼠87只随机分为对照组和低、中、高剂量铅染毒组,分别为21,21,22,23只。各组母鼠通过饮水分别饲以0,0.22,0.67,2.00 mg/ml的醋酸铅水溶液;出生后第2l天起,各组仔鼠则直接饮用与相应母鼠相同浓度的醋酸铅水溶液。于第1,20,40,60,80天各取3只仔鼠海马组织,采用Western Blots方法,以磷酸化抗体检测细胞外信号调节激酶2(ERK2)活力;剩余仔鼠在第80天开始进行水迷宫实验。结果铅染毒仔鼠的定位航行能力和空间搜索能力明显下降,并呈剂量—效应关系;对照组仔鼠海马CA1区ERK2活力随着仔鼠增长其活力明显升高,但到出生后第60天时则达到最高,到第80天略有下降;低剂量组则在第20天时活力明显升高,而在随后的60天里活力明显下降;中、高剂量组酶活力则一直维持在较低水平。以各组第1天的ERK2活力为100,则对照组和低、中、高剂量铅染毒组在第80天时ERK2活力分别为151.3±12.1,129.3±9.1,101.0±8.1,103.0±13.5(中、高剂量组与对照组比较,P<0.01)。结论铅染毒可以扰乱不同发育期大鼠海马CA1区ERK2的活力变化,这很可能是大鼠铅染毒导致空间学习记忆损害的分子机制。更多还原

【Abstract】 Objective To investigate the impairment mechanism of lead exposure on rat spatial learning and memory.Methods 87 Wistar rats,one day after born,were randomly divided into four groups,i.e.control group,low,medium and high dose groups,with 21,21,22,23 rats in relevant groups.In each group,the dams were fed with 0,0.22,0.67,2.00 mg/ml lead acetate water solution respectively as the drinking water.After weaning at postnatal 21 d,the pups were directly fed with lead acetate solution as the drinking water as their dams.Hippocampus tissues from three pups at postnatal 1,20,40,60 and 80 d in each group were collected,the activity of ERK2 was detected by the Western Blots method with phosphorylation antibody.Beginning from the 80th day,the rest pups were trained in a spatial task using water maze.Results Lead exposure could impair position navigation performance of rats and prevent the development of selective searching strategy in dose-effect manner.The ERK2 activity in pups of the control group increased rapidly as they grew and reached maximum at the 60th d.Then the activity began to decline slightly at the 80th d.In the low dose group the activity distinctively elevated at the 20th d,and significantly lowered at the 60th d.As to the medium and high dose groups,the activities sustained in a rather low level.Taking the activity of ERK2 in one day for every group as 100,the activities of four groups at the 80th d were 151.3±12.1,129.3±9.1,101.0±8.1,103.0±13.5 respectively(P<0.01).Conclusions The results indicate that the lead exposure could disturb the normal change of ERK2 activity in different development stages of rats.This might be the molecular mechanism of the impairment of rat spatial learning and memory induced by lead exposure.更多还原