摘要目的 探讨外源性甲状腺素对创伤性脑损伤(TBI)大鼠中枢神经再生修复的作用.方法 选择108只雄性SD大鼠,按随机数字表法分为A组(正常组)、B组(甲状腺素组)、C组(TBI组)、D组(TBI+甲状腺素低剂量组)、E组(TBI+甲状腺素中剂量组)及F组(TBI+甲状腺素高剂量组),每组18只.参照Feeney法建立TBI动物模型,伤后6hA组和C组予生理盐水灌胃,B、D、E及F组分别予10 μg/kg、6.5 μg/kg、10 μg/kg、15.4 μg/kg甲状腺素灌胃.伤后1,3,7d各组按随机数表法选6只大鼠取脑组织.观察脑组织病理形态改变,并分别采用RT-PCR及免疫组化法检测Wnt3a和β-连接蛋白mRNA及脑源性神经营养因子(BDNF)和神经生长因子(NGF)的表达.结果 (1)A组及B组脑组织无病理改变;D、E、F组脑组织病理改变较C组明显减轻,并以E、F组作用更为明显.(2) RT-PCR显示,与C组比较,D组海马中Wnt3amRNA和β-连接蛋白mRNA的表达在伤后7d明显升高(Wnt3a mRNA:6.46±2.02∶4.08±1.06,β-连接蛋白:13.53 ±1.64∶2.11 ±0.63)(P＜0.05);E、F组Wnt3a mRNA表达在伤后3,7d明显升高(E组:5.45±1.54∶2.78±1.04,8.59±1.88∶ 4.08±1.06,F组:5.40±1.38∶ 2.78±1.04,8.63±1.74∶ 4.08±1.06) (P ＜0.05),B-连接蛋白mRNA表达在伤后1,3,7d均明显升高(E组:3.10±0.59∶1.45±0.28,5.28 ±0.62∶1.45 ±0.28,4.12±0.43∶ 1.64±0.31,F组:8.78±0.92∶1.64 ±0.31,23.80±2.38∶2.11±0.63,25.94 ±3.79∶2.11±0.63) (P ＜0.05);而B组海马中Wnt3a mRNA和β-连接蛋白mRNA的表达无明显改变.(3)免疫组化显示,B组海马中BDNF和NGF表达无明显改变;D组BDNF和NGF无明显改变,而E、F组BDNF和NGF明显高于C组,并在伤后3d达到高峰[BDNF:(77.3±5.4)个∶(55.0±5.6)个、(78.0±7.8)个∶(55.0±5.6)个,NGF:(83.7±5.8)个∶(62.2±10.3)个、(86.8±4.8)个∶(62.2±10.30)个](JP＜0.05).结论 外源性甲状腺素对正常大鼠Wnt/β-连接蛋白通路无影响.TBI后外源性甲状腺素能够明显促进中枢神经再生修复,可能与其上调通路mNRA的表达和增加BDNF及NGF的分泌有关.

abstractsObjective 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.