甲状腺功能减退对新生早期大鼠各脑区甲状腺激素受体mRNA表达的影响

Effects of hypothyroidism on expression of thyroid hormone receptor mRNA during rat cerebral development

目的探讨甲状腺功能减退（甲减）对新生早期大鼠各脑区甲状腺激素受体（TR）mRNA表达的影响。方法建立甲减Wistar大鼠动物模型，分别于仔鼠0、14、21、45d，用实时荧光定量PCR方法检测大脑、小脑、脑干和海马TR mRNA的表达。结果与对照组相比，各时间点甲减仔鼠各脑区TRα1 mRNA的表达量呈总体下调趋势，而甲减0d仔鼠大脑、小脑、脑干TRα2 mRNA表达量明显增高（t=8．18、6．23、3．68，P〈0．01），且45d仔鼠各脑区TRα2 mRNA表达量仍高于对照组（t大脑=5．50、t小脑=5．46、t脑干=4．10、t海马=11．83，P〈0．01），TRα1、TRα2 mRNA表达峰（21d）均延迟于对照组（14d）出现。甲减仔鼠TRβ1 mRNA表达变化趋势与对照组相一致，但45d仔鼠各脑区TRβ1 mRNA表达量均低于对照组（t大脑=4．64、t小脑=2．73、t脑干=3．90、t海马=5．07，P〈0．01或〈0．05）。结论甲减时甲状腺激素受体mRNA表达峰值的延迟出现以及异常的表达变化与克汀病脑损伤机制密切相关。

Objective To study the effects of hypothyroidism on the expression of thyroid hormone receptor（TR） isoforms mRNA during rat cerebral development. Methods Neonatal hypothyroidism was induced by the administration of propyhhiouracil （PTU） solution to the dams by gavage（1% PTU,2.5 ml/d） on the embryonic day 15. Brain were collected from the control and hypothyroid rats on postnatal day 0,14,21,45. Real time fluorescence quantification PCR was used to analyze thyroid hormone receptor α1, α2 and β1 mRNA expression between the euthyroid and hypothyroidism rat brain. Results Compared with the euthyroid rat brain,the level of TRα1 mRNA of hypothyroidism rat decreased in cerebrum, cerebellum,hippocampi ,brain stem ,while the level of TRα2 mRNA increased in newborn cerebrum, cerebellum, brain stem and brain areas of 45 days old rat（P 〈 0.01 ）. TRα1 ,TRα2 mRNA peak values were delayed in each areas. TRI31 mRNA decreased in each areas in 45 days old rat （P 〈 0.01 or P 〈 0.05）. Conclusions The abnormal expression of TR isoforms is closely related with the pathogenesis of cretin brain injury.