Effect of exogenous thyroxine on regeneration and repair of central nervous system in rats with severe traumatic brain injury / 中华创伤杂志

ABSTRACT

Objective To investigate the effect of exogenous thyroxine on the regeneration and repair of central nervous system in rats with severe traumatic brain injury.Methods A total of 108 male SD rats were randomly divided into Group A (normal group),Group B (thyroxine group),Group C (TBI group),Group D [TBI + low dose of thyroxine (6.5 μg/kg) group],Group E [TBI + medium dose of thyroxine (10 μg/kg) group)] and Group F [TBI +high dose of thyroxine (15.4 μg/kg)] by random number table method,with 18 rats in each group.The animal model was established according to the Feeney method.Groups A and C were given saline and thyroxine 6 hours after TBI.At 1 day,3 days and 7 days after injury,six rats were selected from each group according to random number table method for brain tissue harvest.The pathological changes of brain tissues were observed,and the expressions of Wnt3a and β-catenin,brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detected by RT-PCR and immunohistochemistry respectively.Results (1) There were no pathological changes in brain tissue in Groups A and B.The pathological changes in brain tissue of TBI rats in Groups D,E and F were significantly mitigated than those in Group C,and the effect of Groups E and F were more obvious.(2) RT-PCR showed that the expressions of Wnt3a and β-catenin mRNA in hippocampus of Group D at 7 days after injury were significantly higher [(6.46±2.02) vs.(4.08 ±1.06);(13.53 ±1.64) vs.(2.11 ±0.63);P＜0.05);Wnt3a mRNA expression of Groups E and F were increased significantly at 3 days and 7 days after injury [(5.45 ± 1.54) vs.(2.78±1.04),(8.59±1.88) vs.(4.08 ±1.06),(5.40±1.38) vs.(2.78±1.04),(8.63±1.74) vs.(4.08± 1.06);P ＜ 0.05)].The expressions of β-catenin mRNA were increased significantly at 1 day,3 days,and 7 days after injury [(3.10 ± 0.59) vs.(1.45±0.28),(5.28±0.62) vs.(1.45±0.28),(4.12±0.43) vs.(1.64± 0.31),(8.78±0.92) vs.(1.64±0.31),(23.80±2.38)vs.(2.11±0.63),(25.94±3.79) vs.(2.11 ± 0.63);P ＜ 0.05)].The expressions of Wnt3a and β-catenin in hippocampus of Group B did not change significantly.(3) Immunohistochemical staining showed that the expression of BDNF and NGF in hippocampus of B did not change significantly after thyroxine treatment,but that of BDNF and NGF in Group D did not change significantly after treatment.The expressions of BDNF and NGF of Groups E and F were significandy higher than that in Group C and reached the peak at 3 days after injury [BDNF(77.3 ± 5.4) vs.(55.0 ± 5.6),(78.0 ± 7.8) vs.(55.0±5.6);NGF(83.7±5.8) vs.(62.2±10.3),(86.8±4.8) vs.(62.2 ±10.3);P＜0.05].Conclusions Exogenous thyroxine has no effect on the Wnt/β-catenin pathway in normal rats.But exogenous thyroxine can significantly promote the centralis regeneration and repair in TBI rats,which might be associated with its role in upregnlating the expression of mRNA and increasing the secretion of BDNF and NGF.