【摘要】 目的探讨铅暴露对不同发育阶段子代小鼠海马中谷氨酸转运体GLAST、GLT-1表达的影响。方法将24只清洁级妊娠昆明小鼠随机分为对照(蒸馏水)组及0.5、1.0、2.0 g/L乙酸铅暴露组,每组6只。母鼠从妊娠第1天至断乳前(出生后21 d)、仔鼠从断乳至出生后40 d(postnatal day,PND40),采用自由饮水方式进行染毒。分别于PND10、PND20和PND40,测定脑组织中铅含量及海马组织中GLAST和GLT-1 m RNA和蛋白的表达水平。结果与对照组比较,2.0 g/L乙酸铅暴露组PND10仔鼠和1.0、2.0 g/L乙酸铅暴露组PND20仔鼠及各浓度乙酸铅暴露组PND40仔鼠脑组织中的铅含量均较高,仅1.0、2.0 g/L乙酸铅暴露组PND40仔鼠海马组织中GLAST m RNA的表达水平均较低,仅2.0 g/L乙酸铅暴露组PND40仔鼠海马组织中GLT-1 m RNA的表达水平较低,仅1.0、2.0 g/L乙酸铅暴露组PND20和PND40仔鼠海马组织中GLAST蛋白的表达水平均较低,仅2.0 g/L乙酸铅暴露组PND10仔鼠及1.0、2.0 g/L乙酸铅暴露组PND20和PND40仔鼠海马组织中GLT-1蛋白的表达水平较低,差异有统计学意义(P<0.05)。随着乙酸铅暴露浓度的升高和暴露时间的延长,不同发育阶段仔鼠的脑组织中的铅含量均呈上升趋势,海马组织中GLAST和GLT-1 m RNA和蛋白的表达水平均呈下降趋势。结论饮水铅暴露可通过抑制不同发育阶段仔鼠海马中GLAST和GLT-1的表达,干扰发育早期仔鼠海马中Glu的转运与代谢,进而可影响突触信号的转导过程,这可能是铅导致学习记忆损伤的机制之一。更多还原

【Abstract】 Objective To investigate the effects of lead exposure on the expression of glutamate/aspartate transporter(GLAST)and glutamate transporter-1(GLT-1) in the hippocampus of mice at the early developmental stages. Methods Twenty-four pregnant mice were randomly divided into control group,0.5,1.0 and 2.0 g/L lead acetate exposed group,six in each group.The pregnant mice were given lead acetate through drinking water from the first day of gestation to weaning(about postnatal day 21),and the pups from weaning to postnatal day 40 drank the same water. Lead levels in the brain and the expression of GLAST and GLT-1 in the hippocampus of PND 10,20 and 40 mice were measured. Results Compared with control group,lead content in brain tissue were increased for PND 10 mice in 2.0 g/L lead acetate exposure group,PND 20 mice in 1.0,2.0g/L lead acetate exposure groups, and PND40 mice in each lead exposure group.The expression levels of GLAST m RNA were decreased for PND 40 mice in 1.0,2.0 g/L lead acetate exposure groups. The expression level of GLT-1 m RNA was decreased for PND 40 mice in 2.0 g/L lead acetate exposure group. The levels of GLAST protein were decreased for PND 20 and 40 mice in 1.0,2.0 g/L lead acetate exposure group. The levels of GLT-1 protein were decreased for PND 10 mice in 2.0 g/L lead acetate exposure group, as well as PND 20 and PND 40 mice in 1.0,2.0 g/L lead acetate exposure group. With the increases of lead concentrations in drinking water and the prolongation of exposure time,lead levels in brain tissue of lead-exposed mice increased,whereas the protein and m RNA levels of GLAST and GLT-1 in hippocampus decreased. Conclusion Lead exposure through drinking water may inhibit the expression of GLAST and GLT-1 in hippocampus of mice at the translational level,which may interfere with the transportation and metabolism of glutamate in synaptic cleft,and thus affect synaptic signal transduction processing.This may be one of the mechanism for damage of learning and memory induced by lead exposure.更多还原