DEHP暴露对子代大鼠空间学习记忆能力和海马突触可塑性相关蛋白基因表达的影响  

Effects of DEHP exposure on spatial learning and memory of offspring rats and on expressions of hippocampal synaptic plasticity related genes in rat's hippocampi

作　　者：王永俊[1,2] 李永宁[2] 马宁[2] 贾旭东[2] 

机构地区：[1]中国疾病预防控制中心营养与健康所,北京100050 [2]国家食品安全风险评估中心卫生部食品安全风险评估重点实验室,北京100021

出　　处：《中国食品卫生杂志》2015年第3期237-241,共5页Chinese Journal of Food Hygiene

基　　金：国家自然科学基金(81202212)

摘　　要：目的通过哺乳期暴露邻苯二甲酸二（2-乙基己基）酯（di-2-ethylhexyl phthalate,DEHP）,研究DEHP对子代SD雄性大鼠空间学习记忆能力和突触可塑性相关蛋白基因表达的影响,初步探讨其机制。方法成熟SD大鼠妊娠后随机分为溶剂对照组（橄榄油）、DEHP低剂量组（5 mg/kg BW）、中剂量组（50 mg/kg BW）和高剂量组（500mg/kg BW）。分娩后第1天至断乳,母鼠经口连续灌胃染毒21 d。待子代大鼠出生后第65~70天,进行Morris水迷宫测试;Real-Time PCR法检测海马突触可塑性相关蛋白基因mRNA的表达情况。结果 Morris水迷宫定位航行试验中,500 mg/kg BW剂量组潜伏期比对照组长,差异有统计学意义（P〈0.05）;在空间探索试验中,500 mg/kg BW剂量组在目标象限路程百分比、目标象限停留时间百分比、穿越平台次数方面,与对照组相比有所降低,差异均有统计学意义（P〈0.05）。Real-Time PCR结果显示,暴露于50、500 mg/kg BW组雄性子代大鼠海马内突触可塑性相关蛋白基因PSD95、CREB、PKA、CAMKII mRNA表达水平下调（P〈0.05）;500 mg/kg BW剂量组海马内突触可塑性相关蛋白基因BDNF mRNA表达水平下调（P〈0.05）。结论一定剂量DEHP哺乳期暴露,可影响子代大鼠的神经系统发育,对空间学习记忆能力造成损害。海马内突触可塑性相关蛋白基因PSD95、CREB、PKA、CAMKII、BDNF mRNA表达受到抑制,可能是其发生作用机制之一。Objective The purpose is to evaluate the effects of di-2-ethylhexyl phthalate （DEHP） on the spatial learning and memory of offspring rats and on expressions of hippocampal synaptic plasticity related genes in rat＇s hippocampi by lactation exposure and explore the molecular mechanism of this process. Methods Mated female rats were assigned to four groups of 8 animals each based on a weight-balanced random allocation scheme after copulation. Mated female rats were administered different concentrations of DEHP （0, 5, 50, 500 mg/kg BW） by oral gavage with a metal catheter from PND 1 through PND 21. Spatial learning and memory were measured continuous 6 days for young adults （PND 65 days to 70 days） with Morris water maze and the effects on expressions of hippocampal synaptic plasticity related genes mRNA in rats＇ hippocampi were detected by Real-Time PCR. Results In the location-navigation test in Morris maze, the latency time of 500 mg/kg BW group was longer than control group, and there was statically significant difference （P 〈 0.05）. In the spatial probe test, the distance percent in the target quadrant, time percent spent in the target quadrant and the frequency of crossing platform of 500 mg/kg DEHP group were less compared with control group （ P 〈 0. 05 ）. According to the data of Real-Time PCR, comparing with control group, the expressions of hippocampal synaptic plasticity related PSD95, CREB, PKA and CAMKII mRNA in 50 and 500 mg/kg BW groups were significantly down-regulated respectively （P 〈 0.05 ）. The expression of hippocampal synaptic plasticity related BDNF was down-regulated in 500 mg/kg DEHP group compared with control group （ P 〈 0. 05 ）. Conclusion Lactation exposure to DEHP （500 mg/kg BW） could produce developmental neurotoxicity and has effect on spatial learning and memory of offspring rats. The inhibition of expressions of hippocampal synaptic plasticity related genes such as PSD95, CREB, PKA, CAMKII and BDNF could be the mechanism of this process.

关 键 词：邻苯二甲酸二(2-乙基己基)酯 塑化剂 大鼠 哺乳期暴露 空间学习记忆 突触可塑性 基因表达 

分 类 号：R114[医药卫生—卫生毒理学]