碘过量对自身免疫性甲状腺炎大鼠子代脑发育的影响及作用机制研究

In recent years,iodine deficiency disorders (IDD) have been effectively controlled, however,the prevalence of autoimmune thyroiditis (AIT)tendstoincrease, especially iniodine sufficient and excess areas due to iodine supplementation.Our group also found that both lactating and pregnant women in areas with excessive water iodine contentaremorelikelyto develop AIT than in iodine sufficient areas.More and more attention had been paid tothe impact of iodine excess on offspring’s brain development with the increasing number of pregnant women with AIT.Brain Derived Neurotrophic Factor (BDNF) is one of the key targets of brain developmentregulated by thyroid hormones, and it can exert many biological functions through combing with its specific receptor, Tyrosine protein kinase B (TrkB). Therefore, in this study we intend to establish a series of AIT animal models with different doses of iodine and apply modern molecular biology combined with electrical physiological technique to observe the related factors of BDNF/TrkBsingal pathway in hippocampus of the rats’ offspring, the induced effects of synaptic long-term potentiation (LTP) in hippocampus and the learning and memory function.Our objective is to discuss the effects of excessive iodine intake on brain development of AIT rats’ offspring and research the mechanism of cerebralfunctioninjury at the synapse and molecular level.In brief, there will be agreat significance for revealing the effects of iodine excess on brain developmentof the offspring.

近年在有效控制碘缺乏病的同时，自身免疫性甲状腺炎（AIT）有增加趋势，特别是在补碘至碘超足量和碘过量地区，发病率显著增加，本课题组在高水碘地区调查中也发现高水碘地区哺乳妇女和孕妇AIT发病率均高于适碘地区。随着AIT妊娠妇女日渐增多，碘过量对其后代脑发育的影响将会越来越被人们所关注。脑源性神经营养因子（BDNF）是甲状腺激素调节脑发育的重要靶分子之一，它与其特异性受体酪氨酸蛋白激酶B(TrkB)相结合在脑内发挥多种生物学功能。本课题拟建立不同碘过量AIT动物模型，采用现代分子生物学和电生理实验技术相结合的方法观察AIT子代大鼠海马BDNF/TrkB信号通路相关因子、海马突触长时程增强效应的诱发效果及评价其学习记忆能力等方面，旨在探索过量碘摄入对AIT大鼠子代脑发育的影响程度，从突触和分子水平研究脑功能损害的神经生化机制，为揭示碘过量对子代脑发育影响提供更深入的分子机制方面的实验依据。

本项目建立EAT动物模型，并给于一定量的碘刺激，从子代脑海马组织形态，脑内单胺类神经递质含量、甲状腺激素受体水平，脑海马组织中BDNF-TrkB信号通路相关因子表达水平以及学习记忆能力方面，探索过量碘致EAT大鼠子代脑发育的潜在影响，结果显示：（1）随着碘摄入量的升高，EAT大鼠甲状腺组织破坏程度及炎性浸润程度加重，TGAb和TPOAb含量明显升高；（2）碘致EAT大鼠的子代在新生儿时期，脑海马CA1区神经元数量减少；脑组织内单胺类神经递质NE、DA的含量下降；（3）碘致EAT大鼠的子代在新生儿时期，脑组织中甲状腺激素受体TRα1、TRβ1水平受到影响，随着患EAT的母鼠碘摄入量增加，其脑组织中甲状腺激素受体TRα1 mRNA的表达水平降低；（4）碘致EAT大鼠的子代在新生儿时期，脑组织中DNA甲基转移酶1 mRNA表达水平显著下降；（5）碘过量致EAT大鼠的子代在幼年时期，脑海马中BDNF-TrkB信号通路可能受到损伤，引起BDNF、TrkB、Ras、MAPK、MEK和CREB mRNA和蛋白表达水平呈现不同程度的下降。（6）不同碘量致EAT大鼠其后代的学习记忆以及空间探索能力的影响主要表现在幼年时期。本研究为过量碘摄入对患有AIT 妇女的后代脑部发育的影响机制提供线索。

内容获取失败，请点击重试