[目的]观察外源性甲状腺素对胎儿酒精效果对大鼠大脑和小脑发育中脑源性神经营养因子(BDNF)的影响.[方法]选择SD孕鼠,分为酒精组、正常对照组、酒精+T4组.于分娩6h后与其子分开,麻醉后心脏采血,测定血中酒精和甲状腺素水平.3个组新生子鼠分别于生后0,7,14,21,28d(P0,P7,P14,P21,P28)时麻醉处死,采用免疫组织化学染色法观察在大脑皮质中BDNF-阳性神经细胞和小脑皮层中BDNF-阳性浦肯野细胞的分布及形态,另部分小脑组织采用免疫电子显微镜方法观察P14时BDNF.阳性浦肯野细胞的微细结构.[结果]酒精组、酒精+T4组母鼠血液中酒精水平明显高于正常对照组(P〈0.05);酒精+T4组母鼠血液中甲状腺素含量高于酒精组(P〈0.05).P7时酒精+T4组在大脑皮质中BDNF-阳性神经细胞的形态和分布类似于正常对照组,即可观察到长而明显突起的成熟的BDNF-阳性神经细胞,但酒精组中始终未出现.酒精+T4组子鼠P14时出现分布及形态与正常对照组类似的基本单层排列的成熟的BDNF-阳性的浦肯野细胞,但酒精组子鼠始终未出现.P28时酒精组子鼠小脑中BDNF-阳性的浦肯野细胞数较正常对照组和酒精+T4组比较有明显减少,P14时酒精组中仅能观察到不完整的细胞器,酒精+T4组中BDNF邛日性的浦肯野细胞的形态与正常对照组类似,能观察到由平行的颗粒粗面内质网组成的尼斯尔氏体及细胞核周围分布的高尔基体等完整的细胞器.[结论]给予孕期滥用酒精的母鼠外源性甲状腺素能促进其后代大脑皮质和小脑皮层中BDNF的合成,改善胎儿酒精效果所导致的脑发育障碍.
OBJECTIVE To study the effects of exogenous thyroxine on brain derived neurotrophic factor (BDNF) in development of cerebrum and cerebellum of rats with fetal alcohol effect. METHODS Time pregnant SD rats were selected, and that in alcohol, control and alcohol + T4 groups was separated from their offspring at 6 h of delivery, and the blood of heart was selected after anesthesia, and plasma concentrations of alcohol and thyroxine were determined. The rats offspring in 3 groups were sacrificed by anesthesia at postnatal 0,7, 14, 21, 28 d. The morphology and distribution of BDNF-positive neurocytes in cerebral cortex and BDNF-positive Purkinje cells in cerebellar cortex were observed by immunohistochemistry, and the microstructure of BDNF-positive Purkinje cells at postnatal 14 d (P14) were observed by IEM. RESULTS The alcohol concentration was significantly higher in alcohol and alcohol + thyroxine groups than in control group(P〈0.05), and the thyroxine concentration was significantly higher in alcohol + T4 group than in alcohol group ( P 〈 0.05). The morphology and distribution of BDNF-positive neurocytes in cerebral cortex in alcohol + T4 group were very similar to that in control at PT, but no in alcohol group. The morphology and distribution of BDNF- positive Purkinje cells in alcohol + T4 group were very similar to monolayer arrayed mature BDNF-positive Purkinje cells in control patterns at P14, but no in alcohol group. The number of BDNF-positive Purkinje cells decreased significantly in alcohol group than in control and alcohol + T4 groups at P28, and the incomplete organelles were only observed in alcohol group at P14, and the morphology of BDNF-positive Purkinje cells in alcohol + T4 group was similar to that in control group, it was characterized by complete organelle of Nissl body consisted of paralleled rough endoplasmic reticulum and perinuclear located Golgi complexes, etc. CONCLUSION The administration of exogenous thyroxine for pregnant rats with alcohol abuse could