不同碘负荷对小鼠甲状腺钠碘转运体基因表达的影响

Sodium iodide symporter gene expression in thyroid of mice with different iodine intakes

目的旨在探讨不同碘负荷状态下钠碘转运体（NIS）基因表达的变化及其在甲状腺自身调节中的作用。方法取断乳1月龄的Babl／c小鼠按碘摄入量不同分为低碘组、正常碘组、5倍碘组、10倍碘组和50倍碘组，饲养3个月、6个月后处死动物。采用实时荧光定量PCR和免疫组化检测NISmRNA和蛋白表达水平，采用过硫酸铵消化砷-铈催化分光光度法测定甲状腺组织碘含量，采用竞争结合放射免疫分析方法检测甲状腺组织激素水平。结果与正常碘组比较，各月龄低碘组小鼠NISmRNA和蛋白表达显著上调，NIS主要定位于细胞膜，具有运碘功能，甲状腺摄碘功能增强，但长期严重碘缺乏最终导致甲状腺组织中碘含量和甲状腺组织激素水平明显降低；各高碘组NISmRNA和蛋白表达有所下降，呈现随碘摄入量增加表达逐渐减低的趋势，且NIS主要分布于胞浆内，不具备跨膜转运碘的能力，甲状腺摄碘能力显著下降，甲状腺组织中碘含量虽有所升高，但不与碘摄入成平行关系。结论不同碘负荷状态下NIS基因表达的调控可发生在转录、翻译和翻译后水平，NIS基因表达及其活性的调节是机体适应低碘、耐受高碘的一种重要保护机制，是甲状腺自身测节的关键所在。

Objective To investigate the sodium iodide symporter （NIS） gene expression during different iodine intakes and its function in thyroid autoregulation. Methods Babl/c mice were randomly divided into five groups according to their different iodine intake levels：low iodine （LI） , normal iodine （NI）, five-fold iodine （5 HI） ,ten-fold iodine （ 10 HI） and fifty-fold iodine （50 HI）. After three months and six months administration,they were sacrificed and thyroids were excised. The mRNA and protein expression level were determined by real time quantitative PCR and immunohistochemistry respectively. Iodine content in thyroid tissue was measured with spectrophotometry and thyroid hormone level was measured with radioimmunoassay. Results Compared with NI group,NIS mRNA and protein expression was greatly increased in LI groups. Immunohistochemistry analysis indicated that NIS was mostly located at the basolateral membrane of thyrocyte,suggesting the improved activity in transporting iodine. But when faced with long-term and severe iodine deficiency,the iodine content in thyroid was finally decreased,and hormone level lowered. On the other hand, in HI groups NIS mRNA and protein expression was greatly down-regulated. There was a tendency of decreasing NIS gene expression level with increasing doses of iodine intakes. In addition, NIS protein was found mainly in intracellular vesicles,rather than at the cell membrane, suggesting the loss of its activity. The iodine content in thyroid tissue was only slightly increased and was not consistent with the iodine intake levels. Conclusion These findings indicate that NIS may be regulated at transcription, translation and post-translation levels. This phenomenon constitutes a highly specialized intrinsic autoregulatory system that protects thyroid from high doses of iodine, but at the same time ensures adequate iodine uptake for hormone biosynthesis. NIS plays a critical role in thyroid autoregulation mechanism.