The experimental study for the evaluation of the developmental neurotoxicity of tributyltin compounds

将怀孕的ICR小鼠暴露于水中浓度为百万分之0、15或50或食物中浓度为百万分之125的氯化三丁基锡。在出生后1、2和3周处死雄性后代。采用高效液相色谱法测定不同脑区去甲肾上腺素、多巴胺（DA）、二羟基苯乙酸、高香草酸（HVA）、5-羟色胺（5-HT）和5-羟基吲哚乙酸（5-HIAA）的含量。125 ppm组的所有后代出生后立即死亡。与对照组相比，在第一周观察到TBT处理的F1组的体重显著降低。与对照组相比，观察到50 ppm F1组纹状体中DA浓度的显著增加，以及15和50 ppm F1组大脑中HVA浓度和延髓中5-HT浓度的显著增加。在3周龄时，神经递质及其代谢产物可能是发育神经毒性的有用指标。对于母鼠，与对照组相比，在125 ppm组的小脑、髓质、中脑和纹状体中观察到5-HT浓度显著降低。与对照组相比，在125 ppm组的母鼠的小脑、中脑和纹状体中也观察到5-HIAA浓度的显著降低。[^3H]MK-801与N-甲基-D-天冬氨酸（NMDA）的结合水平15 ppm F_1组1周龄和15 ppm、50 ppm F_1组3周龄的F_1受体均显著低于相应的对照组。

Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15, or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at 1, 2 and 3 weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed at the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups at the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control.In the same protocol, the [^3H]MK-801 binding level to N-methyl-D-aspartate (NMDA) receptors siginificantly decreased in the 15 ppm F1 group at 1 week and in the 15 ppm and 50 ppm F1 groups at 3 weeks of age, compared with that in the corresponding control F1 group.