亚慢性染毒苯并ɑ芘对大鼠记忆功能及不同脑区NMDA受体表达的影响
Effects of subchronic exposure to benzoɑpyrene on memory function and mRNA expressions of NMDA receptors in different brain regions in rats
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摘要:
背景 苯并ɑ芘（BaP）具有神经毒性，可以引起人和动物短期空间学习记忆障碍，这与其引起的海马N-甲基-D-天冬氨酸（NMDA）受体表达改变有关。BaP是否引起其他脑区NMDA受体亚基表达水平的改变，并参与BaP诱导的神经毒性目前尚不清楚。
目的 通过亚慢性染毒BaP的SD大鼠模型，观察不同脑区NMDA受体亚基（NR1、NR2A、NR2B）mRNA表达水平，为深入研究BaP神经毒作用机制提供依据。
方法 选择40只SPF级雄性SD大鼠，随机分为对照组和1.00、2.50、6.25 mg·kg−1 BaP染毒组，每组10只，隔日腹腔注射染毒90 d。采用Morris水迷宫检测大鼠寻找平台平均逃避潜伏期、寻找平台平均总路程、平台象限滞留时间。采用实时荧光定量PCR检测海马区、皮质区、小脑区、纹状体NR1、NR2A、NR2B mRNA表达水平。
结果 与对照组相比，2.50、6.25 mg·kg−1 BaP组大鼠平均逃避潜伏期、寻找平台平均总路程延长（P<0.05），6.25 mg·kg−1 BaP组大鼠平台象限停滞时间缩短（P<0.05）。2.50、6.25 mg·kg−1 BaP组海马区NR1、NR2B mRNA表达水平，6.25 mg·kg−1 BaP组NR2A mRNA表达水平均较对照组降低（P<0.05）；6.25 mg·kg−1 BaP组皮质区NR1、NR2B mRNA表达水平，1.00 mg·kg−1 BaP组NR2A mRNA表达水平均较对照组降低（P<0.05）；6.25 mg·kg−1 BaP组小脑区NR2B mRNA表达水平降低（P<0.05）；纹状体NMDA受体各亚基mRNA表达水平差异无统计学意义（P>0.05）。
结论 亚慢性染毒BaP引起的大鼠短期空间学习记忆功能损伤，可能与其引起的大鼠海马区NR1、NR2A、NR2B mRNA表达的下调，皮质区NR1、NR2A、NR2B mRNA表达的改变以及小脑区NR2B mRNA表达下调有关。
Abstract:Background The altered expressions of hippocampal N-methyl-D-aspartate (NMDA) receptors induced by benzoɑpyrene (BaP) causes short-term spatial learning and memory impairment in humans and animals, but whether BaP causes alterations of NMDA receptor subunits in other brain regions and the associated neurotoxic mechanism is still essentially unknown.
Objective To observe the mRNA expressions of NR1, NR2A, and NR2B of NMDA receptor subunits in different brain regions in SD rat model with subchronic exposure to BaP, and to provide a basis for in-depth study of the mechanism of BaP-induced neurotoxicity.
Methods Forty male SD rats were selected and randomly divided into a control group and 1.00, 2.50, and 6.25 mg·kg−1 BaP exposure groups with 10 rats in each group. The exposure rats received intraperitoneal injection of BaP every other day for 90 d.The average latency to platform, the average total distance, and the duration spent in previous quadrant were measured by the Morris Water Maze. Real-time fluorescence quantitative PCR was used to detect the mRNA expressions of NR1, NR2A, and NR2B in hippocampus, cortex, cerebellum, and striatum of rats.
Results The average latency to platform and the average total distance in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly prolonged compared with the control group (P<0.05), and the duration that rats spent in previous quadrant in the 6.25 mg·kg−1 BaP group was significantly shortened (P<0.05). Compared with the control group, the mRNA expressions ofNR1 and NR2B in the hippocampus in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly reduced (P<0.05), and theNR2A mRNA expression in the hippocampus in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); the mRNA expressions ofNR1 and NR2B in the cortical tissue in the 6.25 mg·kg−1 BaP group were significantly reduced (P<0.05), and the mRNA expression ofNR2A in the cortical tissue in the 1.00 mg·kg−1 BaP group was reduced; the mRNA expression of NR2B in the cerebellar tissue in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); there were no differences in the mRNA expressions of NMDA receptor subunits in the striatum tissue (P>0.05).
Conclusion Subchronic BaP exposure can cause short-term spatial learning and memory impairment in rats, which may be related to the down-regulation of mRNA expressions of NR1, NR2A, and NR2B in hippocampus, changes of mRNA expressions of NR1, NR2A, and NR2B in cortical area, and the down-regulation of NR2B mRNA expression in cerebellum.
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