目的探讨砷暴露对子代大鼠中枢神经系统氨基酸递质代谢酶的影响。方法雌性大鼠于受孕后第6天开始以自由饮水方式分别暴露0、10、50、100mg/L的NaAsO2水溶液,连续染毒直到仔鼠出生后第42天,分别于仔鼠出生后0、28、42d取皮质、海马进行谷氨酰胺脱羧酶(GAD)和γ-氨基丁酸转移酶(GABA—T)mRNA表达检测。结果仔鼠出生后第0天,各染砷组脑组织GAD65、GAD。mRNA表达均未发生变化,GABA—T mRNA表达水平也未发生明显改变。在出生后第28天,100mg/L染砷组仔鼠海马的GAD65和皮质的GAD。mRNA表达水平升高,而50mg/L染砷组仔鼠皮质的GABA—T mRNA表达下降。出生后第42天.100mg/L染砷组仔鼠皮质、海马的GAD65 mRNA表达均增强,海马的GAD。mRNA表达也增强,而GABA—T mRNA表达水平未见明显变化。结论从胚胎到出生后连续的饮水砷暴露能够使GAD。GAD。mRNA表达增强,从而可能会导致脑组织中相关神经递质水平发生改变,引起中枢神经功能紊乱。
Objective To explore the effects of inorganic arsenic on amino acid transmitters of the central nervous system in offspring rats. Methods Wistar rats were exposed to arsenite(0, 10, 50, 100 mg/L, respectively in drinking water) from the 6^th gestation day till F1 pups being 42 days old. The gene expression of GADu, GAD6v and GABA-T in rat brain regions such as cortex and hippocampus were separately determined in F1 pups of 0, 28, 42 days old. Results On the postnatal day 0, there were not any significant changes of GADu, GAD67 and GABA- T mRNA expression in arsenic rats compared to control rats. However, mRNA expression level of GADu in hippocampus and GAD67 in cortex significant increased in rats exposed to 100 mg/L arsenic compared to control rats on the postnatal day 28, but mRNA expression level of GABA-T in cortex showed a decrease in rats exposed to 50 mg/L arsenic compared to control rats. On the postnatal day 42, mRNA expression level of GAD increased in cortex and hippocampus in rats exposed to 100 mg/L arsenic exposure rats and mRNA expression level of GAD67 in hippocampus also increased. Conclusions Continuous arsenic exposure from embryo to postnatal could induce the increase of GAD65, GAD67 mRNA expression in the offspring brain, which might result in related changes of r concentration and modify central nervous system metabolism and function.