出生后早期暴露狄氏剂对小鼠纹状体突触发育的影响  

Effects of early postnatal exposure to dieldrin on synaptic development of striatum in mice

作　　者：高晔[1] 王取南[1] 吴珊[1] 

机构地区：[1]安徽医科大学卫生毒理学系,合肥230032

出　　处：《中华劳动卫生职业病杂志》2012年第2期97-102,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金资助项目（30571585）;安徽省自然基金资助项目（050430802）

摘　　要：目的 探讨出生后早期接触狄氏剂后对ICR小鼠哺乳期、青春期和成年期纹状体突触发育的影响.方法 出生后每窝小鼠数量经调整后,随机分为5组,分别为0.2、2.0和20.0 μg/kg 3个狄氏剂染毒组及溶剂对照组和生理盐水组,于出生后第3天（PND3）进行腹腔注射染毒,隔天1次,连续6次,分别在哺乳期（PND14）、青春期（PND36）和成年期（PND98）分离纹状体.采用免疫印迹法检测纹状体相关突触蛋白水平.结果 出生后早期狄氏剂染毒,在哺乳期可降低小鼠纹状体中生长相关蛋白（ GAP43）水平,且存在剂量依赖性；至青春期,纹状体中胶质原纤维酸性蛋白（GFAP）水平升高,酪氨酸羟化酶（TH）、GAP43和突触后致密蛋白（PSD95）水平均较溶剂对照组下降,存在剂量-效应关系,同时在雄性小鼠中还出现突触蛋白Ⅰ （Synapsin Ⅰ）水平下降；GFAP、TH和PSD95的这种改变一直持续到成年以后.结论 出生后脑发育关键期接触狄氏剂可影响小鼠纹状体中GAP43水平,在此后的生命阶段（包括青春期和成年期）,小鼠纹状体中多巴胺能神经元特异性蛋白（TH）和PSD95水平均下降,说明出生后早期短期接触低剂量狄氏剂会持久性干扰纹状体的突触发育.Objective To investigate the effects of early postnatal exposure to dieldrin on striatum synaptic development in lactation,adolescence and adulthood of mice.Methods The pups were divided into 5 groups randomly.Three groups were exposed to dieldrin （0.01% DMSO solution） at doses of 0.2,2.0 and 20.0 μg/kg and two control groups were exposed to DMSO or saline by intraperitoneal injection of every other day from postnatal days （PND） 3 to PND13.The striatum were isolated from brain in lactation （PND14）,adolescence （PND36） and adulthood （PND98）.Western blot assay was used to detect the expression levels of striatal synaptic proteins.Results The postnatal exposure to dieldrin could reduce the level of growth associated protein （GAP43） of striatum in lactation in a dose-dependent manner.In adolescence,the level of glial fibrillary acidic protein （GFAP） in striatum increased and the levels of tyrosine hydroxylase （TH）,GAP43 and post-synaptic density protein 95 （PSD95） decreased with exposure doses.The level of Synapsin Ⅰ decreased in adolescence male mice.The changes of expression levels of GFAP,TH and PSD95 proteins lasted to adulthood.Conclusion Early postnatal exposure to dieldrin could affect the expression level of GAP43 protein in striatum.The expression levels of TH and PSD95 proteins in striatum decreased in adolescence and adulthood.These results indicated that the early postnatal exposure to dieldrin may persistently interfere in the striatal synaptic development.

关 键 词：狄氏剂 纹状体 突触发育 

分 类 号：R722[医药卫生—儿科]