正常和病理甲状腺细胞碘转运体表达及其调控的研究

The active transport of iodide into the thyroid is the first key step for thyroid hormone biosynthesis, which is mediated by the Sodium Iodide Symporter(NIS) at the apical membrane. After molecular cloning of NIS both from rat and man, its function in the physiological and pathological process of thyroid have been fully investigated. Advanced molecular and biochemistrical methods such as cell culture、immuno-histochemistry、RT-PCR、Western-Blot、ELISA and hybridoma were applied to observe the NIS expression in normal and pathological thyroid glands and the influence of hormones、retinoic acid、iodine and cytokines on NIS mRNA expression in thyroid cells, to detect serum NIS autoantibody levels in patients with autoimmune thyroid diseases, to prepare NIS monoclone antibody, and study the significance of NIS in the pathogenesis of thyroid diseases. The study showed that(1)The NIS expression was quite different in thyroid disorders, NIS mRNA could not be detected in thyroid carcinoma tissues except the adjacent normal thyroid tissues, the level of NIS mRNA was highly increased in GD thyroid tissues, while decreased and even undetectable in HT samples. (2) Thyroid regulating factors such as hormones、retinoic acid 、cytokines and iodide could influence NIS expression. The NIS gene expression was elevated by TSH and all-trans retinoic acid, while inhibited by testosterone、dexamethasone、estrogen、TNF-α、IL-6、INF-γand iodine.(3)The level of NIS antibody was significantly higher in GD than healthy subjects and HT patients，while there is no difference in HT patients and healthy subjects.(4)The NIS monoclone antibody was prepared successfully.This study not only revealed the important role of NIS in the pathogenesis of thyroid diseases, but also clarified the regulating effect of hormones、retinoic acid、cytokines and iodide on NIS expression, which boarden the understanding of thyroid homeostasis and pathogensis of AITD. The preparation of NIS monoclone antibody made a solid foundation for further study of its function from protein level.

采用细胞培养、定量RT-PCR、Northern及蛋白印迹等方法，从核酸及蛋白质水平研究正常和病理甲状腺细胞或细胞株表达碘转运体的特征，分析TSH、碘、细胞因子、生长蜃印⑸窬葜始凹鬃聪偬匾煨钥固宥缘庾颂灞泶锏牡骺靥氐悖教值庾颂逶诩鬃聪偕砉δ艿奈趾筒±碜刺姆⑸械淖饔眉耙庖澹鬃聪偌膊〉暮侠碇瘟铺峁┛蒲б谰荨