高碘通过内质网应激诱导甲状腺功能减退的机制研究
Mechanism of Excess Iodine-Induced Hypothyroidism via Endoplasmic Reticulum Stress
徐杨雨凡 1谢莹1
作者信息
- 1. 苏州大学附属第二医院内分泌科，江苏苏州，215000
- 折叠
摘要
过量碘摄入导致甲状腺细胞损伤，引起甲状腺激素合成与分泌障碍，是甲状腺功能减退的重要诱因。内质网应激是细胞响应稳态失衡的关键过程，高碘暴露可诱发该应激。本研究体外培养人甲状腺滤泡上皮细胞Nthy-ori-3-1，以 5 mM 碘化钾（KI）干预72h构建损伤模型。采用内质网应激抑制剂4-苯基丁酸（4-PBA）预处理24h。结果显示，高碘抑制TSHR及其下游甲状腺激素合成关键基因TG、TPO及NIS表达，且内质网应激标志物GRP78、ATF4和CHOP表达量升高，细胞凋亡率增加。但4-PBA 预处理可降低内质网应激水平，恢复TSHR及下游基因表达，减少细胞凋亡。此外，腺苷酸环化酶激动剂Forskolin虽不能恢复TSHR表达，但可绕过受损的 TSHR 直接激活下游 cAMP 通路，改善TG、TPO、NIS表达。这些结果表明，高碘通过诱发内质网应激损害 TSH-TSHR 信号轴，抑制下游激素合成相关基因表达并促进细胞凋亡。靶向内质网应激可成为防治高碘性甲减的新策略。
Abstract
Excessive iodine intake leads to thyroid cell damage and disrupts thyroid hormone synthesis and secretion, serving as a key contributor to hypothyroidism. Endoplasmic reticulum (ER) stress is a critical cellular response to homeostasis imbalance and can be triggered by high iodine exposure. In this study, human thyroid follicular epithelial cells (Nthy-ori-3-1) were cultured in vitro and treated with 5 mM potassium iodide (KI) for 72 h to establish a damage model. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) was applied as a 24 h pretreatment. The results showed that high iodine inhibited the expression of TSHR and its downstream thyroid hormone synthesis-related genes TG, TPO, and NIS, while increasing the levels of ER stress markers GRP78, ATF4, and CHOP, as well as the apoptosis rate. However, 4-PBA pretreatment alleviated ER stress, restored TSHR and downstream gene expression, and reduced apoptosis. Additionally, although the adenylate cyclase agonist Forskolin failed to restore TSHR expression, it bypassed the damaged receptor to directly activate the downstream cAMP pathway and partially improved the expression of TG, TPO, and NIS. These findings indicate that high iodine impairs the TSH-TSHR signaling axis by inducing ER stress, thereby suppressing hormone synthesis-related gene expression and promoting apoptosis. Targeting ER stress may represent a novel strategy for the prevention and treatment of high iodine-induced hypothyroidism.关键词
内科学/甲状腺功能减退/内质网应激/碘/凋亡Key words
Internal medicine/Hypothyroidism/Endoplasmic Reticulum Stress/Iodine/Apotosis引用本文复制引用
徐杨雨凡,谢莹.高碘通过内质网应激诱导甲状腺功能减退的机制研究[EB/OL].(2026-03-19)[2026-03-20].http://www.paper.edu.cn/releasepaper/content/202603-184.学科分类
内科学
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