单胺类神经递质在碘营养异常致儿童智力损伤中作用研究

Iodine is an essential trace element for human growth and development, which showed "U" type effects on the health of the body. "Scientific iodine intake" was not fully implemented because of geological, economic and other factors in China, and a large number of people suffering from damage by iodine nutrition abnormal. Iodine deficiency is known to cause damage to children's intelligence, and our group found that high iodine can also harm children's intelligence in previous study funded by NSFC as well. However, the mechanisms of iodine nutrition abnormal on intellectual damage were confined to the effects of iodine on thyroid hormones, the relationship between iodine and neurotransmitters was rarely reported. Monoamine neurotransmitter is directly related to children's intelligence, so it is very important to study the relationship between iodine nutrition abnormal and monoamine neurotransmitters for preventing the intellectual damage. This study will focus on studying the effects of iodine nutrition abnormal on thyroid hormone, oxidative stress, monoamine neurotransmitters and the combined effects of iodine and monoamine neurotransmitter gene polymorphism from two aspects of experiments in vivo and epidemiological investigation via ELISA, Taqman single nucleotide polymorphism (SNP) genotyping, and so on, taking the advantage that high iodine, iodine and iodine deficiency areas coexist in Tianjin. This study intends to reveal biological mechanism of iodine nutrition abnormal on intellectual damage, provides a theoretical basis for prevention of the adverse effects of abnormal iodine nutrition and guides "scientific iodine intake".

碘是人体生长发育必需的微量元素，对机体健康呈“U”型效应。目前我国因地质、经济等原因致“科学补碘”难以充分实施，部分人群的健康受碘营养异常影响。已知碘缺乏可损伤儿童智力，而本课题组在以往的国家自然科学基金项目研究中发现高碘也可损伤智力。目前碘损伤智力的机制探讨多限于碘对甲状腺激素的影响，碘与神经递质的关系研究较少。单胺类神经递质与智力密切相关，探讨碘营养异常与单胺类神经递质的关系对预防儿童智力损伤非常重要。本研究拟利用天津市同时存在的高碘、适碘和缺碘地区为研究现场，从人群流行病学调查和体内实验两方面，采用ELISA、Taqman单核苷酸多态性（SNP）分型法等，探讨碘营养异常对甲状腺激素、氧化应激和单胺类神经递质的影响及与单胺类神经递质基因多态性在智力损伤中的交互作用。本研究拟揭示碘营养异常致智力损伤的生物学机制，为预防碘营养异常对机体危害提供理论依据，也可指导更好的“科学补碘”。

碘是人体生长发育必需的微量元素，其对机体健康呈“U”型效应。碘缺乏可对儿童智力造成损伤，而高碘对智力的影响存在争议，且碘营养异常智力损伤机制多局限于碘对甲状腺激素的影响，其它机制报道较少。本研究拟采用ELISA法、Taqman单核苷酸多态性（SNP）分型法等，从体内实验和人群流行病学调查两方面，以探讨碘营养异常对智力损伤与单胺类神经递质的关系。. 体内实验发现，高碘可减轻大鼠体重和大脑等脏器系数，且对大鼠海马组织微观结构产生影响。高碘长期暴露可损伤大鼠学习记忆能力，同时高碘还可引起大鼠血清甲状腺激素水平的异常改变；ELISA结果显示高碘还可显著上调大鼠血清MDA的表达水平，并能明显下调SOD和GSH的水平；随碘浓度升高可引起血清中单胺类神经递质（5-HT、DA、E和NE）的减少。. 人群流行病学调查显示高碘病区儿童尿碘和尿氟水平明显高于对照地区和高碘地区，虽发现高碘地区智力降低，但通过分析未发现尿碘与智力之间关系；高碘病区组儿童的血清FT3值及智力水平低于对照地区和高碘地区，其体内血浆DA和5-HT代谢发生紊乱；相较5-HT、E和NE，DA与智商的关系最明显，且DA与智商存在明显的阈值效应。. 单胺类神经递质基因多态性检测结果中仅在携带COMT AA和GA基因型儿童的智力有差别，年龄-COMT基因型交互作用中携带GA基因型的10~12岁儿童智商的影响最大。其他交互作用只有DRD3 vs 5-HTR2A有意义。DRD2/ANKK1 TaqIA位点基因多态性在高氟暴露儿童的智力上存在调节作用，且TT基因型-氟的交互作用影响智力，5-HTR6 CT基因型和DBH AG基因型在高碘暴露儿童智力上存在负性影响。蛋白组学分析中筛选出19种血浆差异蛋白质，可作为高碘/高氟神经毒性的早期特异性标志物并为阐明智力损伤机理提供参考。. 本研究重点研究碘营养异常对甲状腺激素、氧化应激和单胺类神经递质分泌的影响及与单胺类神经递质基因多态性在智力损伤中的交互作用，揭示了碘营养异常致智力损伤的生物学机制，为预防碘营养异常对机体危害提供理论依据，也可指导碘异常地区“科学补碘”。