胚胎期和哺乳期铅暴露对仔鼠海马代谢型谷氨酸受体5表达的影响  

The effect of lead exposure during early stage of life on expression of metabotropic glutamate receptor subtype 5

作　　者：徐健[1] 颜崇淮[1] 邹向宇[1] 钟乐[1] 余晓刚 

机构地区：[1]上海交通大学医学院附属新华医院上海市儿科医学研究所上海环境与儿童健康重点实验室,上海200092

出　　处：《临床儿科杂志》2010年第1期65-68,72,共5页Journal of Clinical Pediatrics

基　　金：国家自然科学基金资助项目(No.39700121;30070665);上海市科委科技启明星计划资助项目(No.99QB14008);2007教育社科医学研究论文奖计划

摘　　要：目的探讨胚胎期和哺乳期不同程度的铅暴露对断乳仔鼠海马组织代谢型谷氨酸受体5亚型(mGluR5)mRNA和蛋白表达的影响。方法健康成年雌性SD大鼠分为高铅组、中铅组、低铅组和对照组,分别给予0.5%、0.2%、0.05%醋酸铅溶液和双蒸水自由饮水,1周后雌雄合笼,仔鼠断乳时用原子吸收和等离子电感耦合质谱仪测定仔鼠血铅和海马铅含量,用荧光定量PCR和Western blot检测发育脑海马mGluR5mRNA和蛋白的表达水平。结果铅暴露组血铅和海马铅含量高于对照组,且铅暴露剂量越大,血铅和海马铅含量越高(P<0.05)。高铅组、中铅组和低铅组mGluR5mRNA表达量与正常对照组相比下降,比值分别为0.66、0.78和0.82。高铅组、中铅组和低铅组mGluR5蛋白表达较正常对照组下调,铅暴露剂量越高,mGluR5蛋白表达水平越低,差异有统计学意义(P<0.05)。结论海马mGluR5可能参与了铅对神经发育的毒性作用,可能是铅神经发育毒性的中间环节之一。Objective The effect of lead exposure on children is consistently associated with intellectual and other neurologic deficits. However the exact mechanism by which Pb2＋ exerts toxic effects on developmental central nervous system remains unknown. Our group has found by gene-chip test that the expression of metabotropic glutamate receptor subtype 5 （mGluR5） mRNA was changed by lead exposure. The present study aimed to examine the effects of different level of lead exposure on the expression of mGluR5 in gestation and lactation. Methods Sprague-Dawley rats were exposed to lead acetate during gestation and lactation. Three concentrations of 0.05% ,0.2% ,and 0.5% lead acetate were applied and considered as low,middle and high exposure group respectively. The Pb levels of blood and hippocampus of pups were analyzed at weaning to evaluate the actual lead content at the end of the exposure. The impact of lead exposure on the expression of mGluR5 mRNA and protein in hippocampal tissue of pups was investigated by quantitative real-time polymerase chain reaction （PCR） and Western blot. The potential role of the expression of mGluR5 mRNA and protein in lead neurotoxicity were discussed. Results The levels of lead in blood and hippocampus from lead-exposed rats were significantly higher than those in the controls and positively related to the degree of lead exposure. The results of real-time PCR and Western blot showed that exposure to lead acetate decreased the expression of mGluR5 mRNA and protein with a dose-dependent manner. Conclusions Hippocampal mGluR5 might be involved in lead-induced neurotoxicity.

关 键 词：铅 谷氨酸受体 大鼠 定量多聚酶链反应 

分 类 号：R114[医药卫生—卫生毒理学]