新生早期甲状腺功能减退大鼠心肌甲状腺激素受体mRNA表达的实验研究

Expression of thyroid hormone receptor mRNA in the neonatal hypothyroid rat myocardium

目的探讨新生早期甲状腺功能减退（简称甲减）对大鼠心肌发育过程中甲状腺激素受体（TR）各亚型mRNA表达的影响。方法Wistar雌鼠从怀孕15d开始每天经胃灌注1％丙硫氧嘧啶2．5ml，复制甲减仔鼠动物模型，分别于各时间点称体质量后处死仔鼠，取心脏。放射免疫分析法（RIA）动态监测各组大鼠血清FT3、FT4水平，FQ—PCR方法检测各组心肌TR各亚型mRNA的表达差异。结果与对照组比较，甲减大鼠心肌TRα1 mRNA表达量在出生后0、21、45d分别下调90％、15％、36％（tod=8．33，t21d=2．58，t45d=3．25，P〈0．05），表达峰值于生后2周延迟出现。甲减大鼠心肌TRα2 mRNA表达量在出生后0、14、21、45d分别上调22％、72％、82％、36％（t0d=3．89，t14d=11．88，t21d=13．90，t45d=6．19，P〈0．05），表达峰值于生后2周延迟出现。甲减大鼠心肌TRβ1 mRNA表达量在出生后0、14、21、45d分别下调75％、62％、68％、60％（t0d=38．96，t14d=5．22，t21d=17．23，t45d=5．43，P〈0．05），表达变化趋势与对照组一致。结论新生早期甲减大鼠心肌上TR mRNA的异常表达可能与甲减性心脏病的发病机制密切相关。

Objective To study the effects of hypothyroid on expression of thyroid hormone receptor isoforms mRNA in rat myocardium. Methods Neonatal hypothyroidism was induced by the administration of propylthiouracil （PTU） solution to the dams by gavarge （1%PTU,2.5 ml/d） on the embryonic day 15. Hearts were Collected from the control and hypothyroid rats immediately and 14, 21, 45 days after birth. Radioimmunoassay was used to monitor the level of FT3,FT4 in each group. Real time fluorescence quantification PCR was used to analyze thyroid hormone receptor （TR） α1, α2 and β1 mRNA expression diversities between the euthyroid and hypothyroidism rat myocardium. The pathologic alterations of the hypothyroid rat myocardium were observed by hematoxylin-eosin staining. Results TRα1 mRNA in hypothyroid rat myocardium was respectively decreased by 90%, 15% and 36% of euthyroid levels on day 0, 21 and 45（P 〈 0.05）. TRα2 mRNA was increased by 22%, 72%, 82% and 36%of euthyroid levels on day 0, 14, 21 and 45 （P 〈 0.05）, respectively. The magnitudes of the decreased in TRβ1 mRNA were 75%,62%,68%,60% of euthyroid levels in 0 d, 14 d,21 d,45 d hypothyroid rat myocardium（P 〈 0.05）, respectively. Compared with that of euthyroid myocardium, the level of TRα1 and TRα1 mRNA decreased, the level of TRα2 mRNA increased （P 〈 0.01 ）. Furthermore, TRα1 and TRα2 mRNA peak time were postponed. Conclusion The abnormal expression of TR isoforms mRNA is closely related with the pathogenesis of hypothyroidism heart disease.