围产期母鼠染毒双酚A对雄性子代脑内谷氨酸N-甲基-D-天冬氨酸受体发育的影响  

EFFECTS OF PERINATAL EXPOSURE TO BISPHENOL-A ON DEVELOPMENT OF THE N-METHYL-D-ASPARTATE RECEPTOR OF THE MALE OFFSPRING RAT'S BRAIN

作　　者：王亚民[1,2] 徐晓虹[1,2] 张婧[1,2] 罗清清[1] 叶银萍[1,2] 

机构地区：[1]浙江师范大学化学与生命科学学院,金华321004 [2]浙江师范大学生态研究所,金华321004

出　　处：《生物物理学报》2009年第2期99-105,共7页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(30771783;30872087)~~

摘　　要：为了探讨围生期双酚A(bisphenol A,BPA)暴露对雄性子代大鼠海马和前皮层谷氨酸N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate Receptor,NMDAR)表达的影响,作者通过对妊娠第7天至仔鼠出生后21天的母鼠灌胃染毒BPA(200、50、5、0.5mg/kg·d),用Western-blot法分别检测出生后4、7、14、21、56天的雄性仔鼠海马和前皮层NMDA受体NR1、NR2A、2B亚基的表达。结果显示,在海马区,较低剂量(0.5～50mg/kg·d)BPA剂量依赖性地下调NMDA受体各亚基表达,而高剂量(200mg/kg·d)BPA最显著下调NR1表达,却对NR2A、2B的影响最小;但所有BPA剂量组的NMDA受体亚基表达均显著低于对照组。在前皮层,NMDAR亚基表达对BPA的敏感性相对较低,只有较高剂量(50～200mg/kg·d)BPA可明显下调NR2A、2B亚基表达。此外,BPA明显改变NMDAR的亚基组成,NR2A/NR1和NR2B/NR1比值在海马区被200mg/kg·dBPA上调,在前皮层却被0.5mg/kg·dBPA上调;其它剂量BPA均下调两脑区的该比值。以上结果提示,母体围生期双酚A暴露下调NMDA受体表达和亚基组成,这可能是BPA影响雄性子代脑发育的机制之一。The aim of the present study is to investigate the effects of perinatal maternal exposure to bisphenol-A （BPA） on the N-methyl-D-aspartate receptor （NMDAR） expressions in the hippocampus and the premotor cortex of male offspring rats during postnatal development. Dams were orally exposed to BPA dissolved in oil （200, 50, 5 or 0.5 mg/kg·d） or only oil as a vehicle control per day from GD 7 through postnatal day （PND） 21. Western-blotting technique was used to determine the expression of NR1, NR2A, NR2B subunits in the hippocampus and the premotor cortex of male offspring rats at postnatal day （PND） 4, 7, 14, 21, 56. The results showed that, in the hippocampus, the expressions of NMDAR subunits in the all groups of BPA exposure were remarkable decreased when compared with the control group. At the lower dose of 0.5~50 mg/kg·d, BPA concentration-dependently down-regulated the expression of NMDA receptor subunits; however, at the high dose （200 mg/kg-d）, the effects of BPA on these subunits were different, with a larger down-regulation of NR1 expression and a less down-regulation of NR2A, 2B expression when compared with those at the lower dose of BPA. In the premotor cortex, the expression of NMDAR subunits is less sensitive to BPA. Only the higher dose （50, 200 mg/kg-d） of BPA exposure down-regulated the expression of subunits NR2A, 2B. In addition, BPA changed the component of NMDAR subunits in a different pattern in the hippocampus and the premotor cortex. The rates of NR2A and NR1, NR2B and NR1 were increased by 200 mg/kg·d of BPA in the hippocampus, but by 0.5 mg/kg·d of BPA in the premotor cortex; however, the other dose of BPA decreased the rates, when compared with the control. These results suggest that perinatal exposure to BPA down-regulated NMDAR expression and changed the component of NMDAR subunits. This may be one of the mechanisms underlying the effects of BPA on the development of brain.

关 键 词：双酚A NMDA受体 海马 前皮层 

分 类 号：Q735[生物学—分子生物学]