甲状腺激素对大鼠大脑皮质及海马Bcl-2和Bax的影响

The effects of thyroid hormone on Bcl-2 and Bax in the neonatal rat cortex and hippocampus

目的研究甲状腺素（T4）对发育期大鼠大脑皮质、海马细胞Bcl-2和Bax的影响。方法采用甲巯咪唑复制甲状腺功能减退（甲减）孕鼠模型，出生后仔鼠为先天性甲减鼠，T4替代组于仔鼠出生后即日起腹腔注射T4剂量为每天20μg／kg，同时设对照组；采用免疫组化染色检测出生后第7、14、21天仔鼠大脑皮质、海马Bcl-2和Bax蛋白。结果①甲疏咪唑组各日龄仔鼠血清FT3、FT4水平明显低于对照组。②对照组大鼠生后大脑皮质、海马有散在的Bax和Bcl-2阳性细胞，以生后第7天表达较高，此后随日龄增加渐降低，至生后第21天表达已很弱。甲减组各脑区Bcl-2阳性细胞减少，而Bax阳性细胞明显增加。T4替代后Bcl-2阳性细胞明显增加．Bax阳性细胞减少。结论①对照组大鼠发育期大脑皮质、海马Bcl-2和Bax表达阳性，且在不同发育时期表达不一致，至成年动物表达很弱，说明在大鼠正常发育过程中，Bcl-2和Bax呈一定时程变化规律。②甲减时大脑皮质和海马Bcl-2下调、Bax上调，及时T4替代治疗可以增强Bcl-2并降低Bax基因的表达。

Objective To study the effects of thyroid hormone on Bcl-2, Bax in developing rat cortex and hippocampus. Methods Methiamazole（MM） was used to replicate the model of maternal pregnant hypothyroidism. The infant rats were innate hypothyroidism. T4 substitution group rats were administrated with T4 on the first day after birth and ever since. Normal neonatal rats were enrolled as control, immunohistochemical staining technique was employed to detect Bcl-2 and Bax proteins in cortex and hippocampus on the 7th, 14th and 21st days postnatal. Results ①Serum FT3 and FT4 levels of neonatal rats in MM group were significantly lower than those in normal control group; In MM ＋ T4 group, the FT3 and FT4 levels of neonatal rats were significantly higher than those hypothyroid rats on the same day, still below normal levels. ②There were Bcl-2 and Bax-positive cells in cortex and hippocampus of the normal developing rat. The expression of Bcl-2 and Bax were highest on the 7th days postnatal, subsequently decreasing along with age. In MM group, Bcl-2-positive cells decreased and Bax-positive cells increased; while Bcl-2-positive cells increased and Bax-positive cells decreased after T4 supplementation. Condusions ①In developing rat cortex and hippocampus, Bcl-2 and Bax are positive, varying in intensities in different developing stages. In adult rats, their expression is weak. ②Bcl-2 decreases while the Bax expression increases in hypothyroidism. Timely therapy of T4 substitution enhances Bcl-2 gene and reduces Bax gene expression. So It is concluded that different effects of thyroid hormone on Bcl-2 and Bax play an important role in apoptosis. T4 substitution therapy was an important way to inverse hypothyroid brain damage.