硒拮抗补碘诱导的甲状腺损伤的表观遗传学机制研究

Iodine deficiency disorders (IDD) is a global public health problem and China is one of the countries threatened by it most seriously. Universal salt iodization (USI) treats IDD successfully. Meanwhile, iodine-induced thyroid injury draws attention. Relevant reports and our initial work shows that iodine supplementation to iodine-deficient population may increase the risk of hypothyroidism and autoimmune thyroiditis, and selenium can attenuate iodine-induced thyroid injury with mechanism not clear. We hypothesize that selenium antagonizes iodine-induced thyroid injury through epigenetic regulation. Both of iodine-deficient animal model and Fisher rat thyroid cell line will be employed to confirm the iodine-induced thyroid injury. MeDIP-seq and ChIP-seq, being high-throughput and cost-effective methods, will be used to perform genome-wide analysis of methylated DNA and histone modification in thyroid. Bioinformatics analysis, based on the methylated DNA profile and histone code, will establish the specific maps produced by iodine deficiency, iodine supplementation and iodine supplementation together with selenium in thyroid. This project comprehensively evaluates the safety of iodine supplementation and the antagonistic action of selenium against iodine-induced thyroid injury. It provides a new idea for iodine supplementation strategy for iodine-deficient population.

碘缺乏病是全球性的公共卫生问题，我国是受其危胁最为严重的国家之一。在全民食盐加碘治疗碘缺乏病取得成功的同时，补碘诱导的甲状腺损伤逐渐引起关注。相关报道及我们前期工作显示缺碘人群补碘可导致自身免疫性甲状腺炎和甲状腺功能减退症的发病率增加，且补硒能拮抗单纯补碘诱导的甲状腺损伤，但机制不清楚。我们认为硒可通过表观遗传学拮抗补碘诱导的甲状腺损伤。本项目利用缺碘动物模型和甲状腺细胞，在明确补碘引起甲状腺损伤的基础上，运用高效、便捷的甲基化DNA染色体共沉淀和染色体免疫共沉淀测序技术，从DNA甲基化和组蛋白修饰两个不同的角度，探讨硒拮抗补碘诱导的甲状腺损伤的表观遗传学机制；采用生物信息学分析，建立缺碘、补碘及硒碘同补时甲状腺的特征性表观基因组图谱，为寻找相应的分子生物学标志物提供线索。本项目为全面评价补碘的安全性及硒拮抗补碘诱导的甲状腺损伤奠定理论基础，为缺碘人群的补碘策略提供新思路。

碘缺乏病是全球性的公共卫生问题，我国是受其危胁最为严重的国家之一。在全民食盐加碘治疗碘缺乏病取得成功的同时，补碘诱导的甲状腺损伤逐渐引起关注。相关报道及我们前期工作显示缺碘人群补碘可导致自身免疫性甲状腺炎和甲状腺功能减退症的发病率增加，且补硒能拮抗单纯补碘诱导的甲状腺损伤，但机制不清楚。我们认为硒可通过表观遗传学拮抗补碘诱导的甲状腺损伤。本项目利用缺碘饲料建立缺碘动物模型，证实了超足量补碘可导致缺碘动物甲状腺氧化损伤，补碘的同时给予补硒可以拮抗上述损伤，且硒的拮抗作用存在剂量效应关系。运用高效、便捷的甲基化DNA染色体共沉淀和染色体免疫共沉淀测序技术，从DNA甲基化和组蛋白修饰两个不同的角度，探讨硒拮抗补碘诱导的甲状腺氧化损伤的表观遗传学机制；采用生物信息学分析，建立缺碘、超足量补碘及补碘同时补不同剂量硒时甲状腺的特征性表观基因组图谱，为寻找相应的分子生物学标志物提供线索。本项目为全面评价补碘的安全性及硒拮抗补碘诱导的甲状腺氧化损伤奠定理论基础，为缺碘人群的补碘策略提供新思路。