The Effects Of Thyroid Hormone On Programmed Cell Death And The Relative Genes Expression In The Neonatal Rat Brain

Objective To study the effects of thyroid hormone on programmed cell death(PCD) and relative genes Bcl-2,Bax expression in developing rat cortex and hippocampus.Methods In the study,experimental animals were divided into three groups. Thiamazole(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 from postnatal 0 day as well as the same days normal neonatal rats as control. TdT-mediated dUTP nick end labeling(TUNEL) was carried out to detect the positive cells of PCD in cortex and hippocampus of postnatal 7,14 and 21 days rats. Immunohistochemical staining technique was employed to detect Bcl-2 and Bax proteins in relevant sections. Experimental data were statistically analysed by One-Way ANOVA, SNK-q test and Spearman rank correlation analysis. Results (1) Serum 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 in same days hypothyroid rats, but they didn't recover to normal levels. (2) There was PCD in cortex and hippocampus of the normal developing rat. PCD was maximal at postnatal 7 days . Hypothyroidism led to increase of apoptotic cells in every group. After T4 supplementation, the number of apoptotic cells reduced, but it was higher than the normal group. (3) There 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 at postnatal 7 days and it had tendency to descend expression 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. (4)There was a negative correlation between the number of apoptotic cells and the score of Bcl-2/Bax (cortex: r=-0.537, p<0.01; hippocampus: r=-0.391, p<0.01).Conclusions (1)There were PCD in cortex and hippocampus of the normal developing rat. Expression of PCD relative genes Bcl-2,Bax were positive and different in different developing stages. In adult rats, their expression were weak. These showed that there was a changing regularity with days in PCD and relative genes expression during postnatal rats brain development. (2)PCD increased in cortex and hippocampus of hypothyroid rat. It indicated brain function obstacle of hypothyroidism might be related to PCD. (3)The Bcl-2 expression decreased while the Bax expression increased in hypothyroidism. There was a negative correlation between the number of PCD and the score of Bcl-2/Bax. It was concluded that motivating of Bcl-2/Bax apoptotic path was one of mechanisms of PCD increasing in hypothroidism. (4) Timely T4 substitution therapy could strengthen Bcl-2 gene and reduce Bax gene expression and restrained PCD. So it was an important way to correct hypothyroid brain damage.