Effects of neonatal exposure to tributyltin on the rat brain myelination.

三丁基锡（TBT）被认为是一种内分泌干扰物，因为它抑制了雄激素转化为雌激素的芳香化酶。本研究的目的是评价TBT对大鼠神经组织发育的影响。A：TBT的产前暴露（1）妊娠大鼠在妊娠第7天或第14天暴露于TBT。仔鼠出生后第21天取脑。TBT染毒组大鼠的类固醇含量、微粒体组分中P450活性和少突胶质细胞酶CNP（2 '，3'-环核苷酸3 '-磷酸二酯酶）活性与对照组大鼠无显著差异。结果表明，产前暴露于三丁基锡化合物不会影响后代的大脑发育。B：新生大鼠暴露于TBT（1）新生大鼠在出生当天暴露于TBT。在21、35和49日龄收集后代的脑。与对照组相比，各TBT暴露组的新生儿髓鞘CNP活性均显著降低，即使在相对低水平的TBT暴露下也是如此。CNP的Western blot分析显示，在各个发育阶段的酶活性的相似的结果。(2)与对照组大鼠相比，TBT暴露大鼠的主要脑髓鞘蛋白的mRNA水平被选择性地影响。(3)TBT染毒组大鼠脑内糖脂合成糖基转移酶的mRNA水平与对照组基本相同。然而，与对照组大鼠相比，7周龄时TBT暴露大鼠脑中GlcCer合酶和CSE合酶（硫苷脂合酶）的水平显著降低。(4)对TBT暴露大鼠和对照大鼠脑中鞘糖脂和磷脂的TLC图谱进行了检查。(289字）

Tributyltin (TBT) is recognized as an endocrine-disrupting chemical, because of suppressing the aromatase for conversion of androgen to estrogen. The purpose of this study was to evaluate the effect of TBT on development of rat neuronal tissues.A: Prenatal exposure to TBT(1) Pregnant rats were exposed TBT on days 7 or 14 of pregnancy. The offspring brains were collected on the 21st day after birth. Steroid contents, P450 activity in microsome fractions, and the activities of oligodendrocyte enzyme CNP (2', 3'-cyclic nucleotide 3'-phosphodiesterase) in the TBT exposed rats were not significantly different from those in the control rats. Results showed that prenatal exposure to TBT did not affect the brain development of offspring. The fetuses are probably defended from TBT by the placenta.B: Neonatal exposure to TBT(1) Neonatal rats were exposed TBT on the day of birth. Brains of offspring were collected on 21, 35, and 49 days of age. The CNP activities of myelin in all neonatal TBT exposed groups were significantly decreased compared with those of the control groups even in the relatively low level exposure. Western blot analysis of CNP showed the similar results as enzyme activities at each developmental stage. (2) The mRNA levels of major brain myelin proteins of TBT-exposed rats were selectively affected compared with the levels of control rats. (3) The mRNA levels of glycolipid synthesis glycosyltransferases in the brains of TBT-exposed rats were almost same as the levels of control rats. However, the levels of GlcCer synthase and CSE synthase (sulfatide synthase) of TBT-exposed rat brain at 7 weeks of age were remarkably decreased compared with the levels of control rats. (4) TLC profiles of sphingoglycolipids and phospholipids in the brains of TBT-exposed and control rats were examined. (289 words)