十溴联苯醚染毒对大鼠学习记忆及海马NMDA受体的影响

The Effects of Brominated Diphenyl Ether-209（BDE-209） Exposure on Spatial Learning and Memory Abilities and NMDA Receptor in the Hippocampus of Adult Rats

摘要:

目的 探究十溴联苯醚对学习记忆能力的损害机制，为科学制定十溴联苯醚职业暴露预防控制措施提供科学的参考依据。 方法 观察十溴联苯（BDE-209）的神经毒性作用对成年大鼠学习记忆以及海马N-甲基-D天冬氨酸（NMDA）受体的影响，选用符合标准的健康雄性SPF级SD大鼠32只，随机分为溶剂（花生油）对照组和250、500、1 000 mg/kg BDE-209染毒组，共4组，每组8只。采取连续管饲染毒方式，每日1次，管饲周期为30 d。染毒结束后，定位航行、空间搜索实验测试成年雄性大鼠的空间学习记忆能力；RT-PCR法测定海马NMDA受体亚单位mRNA的相对表达水平。 结果 在相同训练时间内，不同剂量BDE-209染毒组大鼠比溶剂对照组大鼠的逃生潜伏期和垮台次数均延长，随着染毒剂量的增高，逃生潜伏期时间越长，垮台次数越少，差异有统计学意义（P < 0.05）；各剂量BDE-209染毒组大鼠海马组织内NMDA受体NR1、NR2B和NR2C亚单位mRNA表达的相对含量均比对照组低（P < 0.05），其中NR1和NR2B亚单位mRNA相对表达量随着BDE-209染毒剂量的增加而降低；与溶剂对照组比较，染毒组大鼠海马NR2A亚单位mRNA相对表达量均下降（P < 0.05）；与溶剂对照、低、中剂量组比较，高剂量组NMDA受体NR2D亚单位mRNA相对表达明显降低（P < 0.05）。 结论 BDE-209染毒导致大鼠学习和记忆能力下降，可能与海马NMDA受体各亚单位mRNA表达下降有关。

Abstract:

Objective To explore the damage mechanism of decabromodiphenyl ether on learning and memory ability，and to provide scientific reference for the formulation of occupational exposure prevention and control measures of decabromodiphenyl ether. Methods Neurotoxic effects of decabromobiphenyl （BDE-209） on learning and memory and hippocampal N-methyl-d aspartic acid （NMDA） receptors in adult rats were observed. A total of 32 SPF male SD rats were randomly divided into 4 groups with 8 rats in each group: solvent （peanut oil） control group and 250，500，1 000 mg/kg BDE-209 exposed group. Continuous tube feeding was administered once a day for 30 days. After exposure，the capability of spatial learning and memory of rats were tested by place navigation and spatial probe tests. RT-PCR was used to identify the mRNA levels of NMDA receptor subunits in the hippocampus in adult rats. Results During the same training time，compared BDE-209-treated rats in different dose groups with the solvent control rats，the times of founding the platform in the BDE-209-treated groups were prolonged in a dose-dependent manner，and the numbers of rats crossed the original platform decreased in a dose-dependent manner too，with significant difference （P < 0.05）. The mRNA expression levels of NR1，NR2B and NR2C subunits in hippocampus of rats exposed to BDE-209 were lower than those in control group. （P < 0.05）. The mRNA relative expression levels of NR1 and NR2B subunit decreased with the increase of BDE-209 exposure dose. Compared with the solvent control group，the mRNA relative expression of NR2A subunit in the hippocampus of rats in the exposed group was decreased. （P < 0.05）. Compared with the solvent control group，low dose group and medium dose group，the mRNA relative expression of NR2D subunit of NMDA receptor in high dose group was significantly decreased （P < 0.05）. Conclusion BDE-209 exposure resulted in decreased learning and memory ability in rats，which may be related to decreased mRNA expression of subunits of NMDA receptor in hippocampus..