多溴联苯醚内暴露对儿童甲状腺激素浓度的干扰及机制研究

Polybrominated diphenyl ethers (PBDEs) are commonly used flame retardants. The PBDEs have thyroid disrupting effect, and are harmful to the growth of the children. The variation of thyroid hormones (THs) levels exposed to PBDEs cries for solution. Based on characters of synthesize, transport, metabolism of THs and previous studies on animal testing, we believe concentration of triidothyrine (T3) decrease, concentration of thyroxine (T4) is decided by synthesis effects of several mechanisms when human exposed to PBDEs. However, there is still a lack of reliable and consistent results to support variation of THs levels when exposed to PBDEs. This should be accused to some hormones which associate with THs cannot be detected from blood. Thus, the present study investigate the concentration of PBDEs, THs and some relevant hormones in children blood, and mRNA expression levels of hormones which cannot directly measured in blood. Based on the analysis of relevant hormones concentrations and their mRNA expression levels, the present study verify the variation of THs levels and its underlying mechanisms in children when exposed to PBDEs. The result of the present study can further explain the toxic mechanisms of PBDEs, and help to formulate policies on health risk management. Furthermore, the result can help to protect children from toxic environment and promote their growth.

多溴联苯醚(PBDEs)是常用的阻燃剂。PBDEs暴露可干扰人体甲状腺功能，严重影响儿童的生长发育，如何解释PBDEs影响下甲状腺激素(THs)的变化是亟需明确的问题。综合THs的合成、转运、代谢特点和前人动物研究结果，本研究推断PBDEs暴露下人体甲状腺激素T3浓度下降，甲状腺激素T4浓度的变化取决于多种机制的相互作用。然而，当前研究对PBDEs影响下THs浓度变化趋势缺乏统一认识，最主要原因是部分影响THs变化的相关激素无法经由血样测定。因此，本研究分析儿童血中PBDEs内暴露浓度、THs及部分相关激素浓度，并对血中难以测定的其它相关激素检测基因表达量；通过对THs与相关激素浓度、基因表达量变化的分析，明确PBDEs暴露下THs的浓度变化及其作用机制。本研究为深入了解环境PBDEs污染健康危害的机制、继而制定环境健康风险管理政策提供依据；还对保护儿童远离毒害、促进儿童健康成长意义重大。

本项目研究了儿童多溴联苯醚（PBDEs）暴露对甲状腺激素（TH）的干扰机制。测定了广东电子垃圾拆解区（57份）和对照区（57份）儿童血 PBDEs、多氯联苯（PCBs）、新型阻燃剂（NFRs）浓度、甲状腺相关激素浓度、基因表达量。发现PBDEs等污染物浓度与促甲状腺激素（TSH）及甲状腺结合球蛋白的浓度、甲状腺激素受体α和β、脱碘酶I（ID1）基因表达量的相关关系具有显著性，这些关联导致暴露组和对照组的TSH浓度、TRα和ID1表达量之间差异具有显著性。这些结果说明PBDEs等污染物对TH的载体、受体、脱碘酶都有干扰，但是这些干扰机制对TH的影响效果不完全相同，甚至有些效应完全相反。暴露组和对照组的TH浓度不存在显著差异，和这些干扰机制的组合和互相抵消有关。对于不同暴露水平、体格和健康状况的人群，上述TH干扰机制的组合和抵消不完全相同，这是前人相关研究结果互相矛盾的原因。本项目还对电子垃圾拆解区（54份）和对照区（58份）成人血样进行了类似的分析，发现PBDEs等污染物对成人TH有类似的干扰机制，但是它们对成人TH的干扰途径比儿童多。..分析了广东石化区儿童（174份）PBDEs和NFRs内暴露水平与TH浓度关系。研究发现PBDEs内暴露浓度与T3浓度显著正相关。发现NFRs内暴露对TH的干扰比PBDEs弱；由于NFRs是PBDEs的替代品，未来这些污染物对石化区儿童TH浓度的干扰可能比现在小。..分析了电子垃圾拆解区和对照区同一人群（成人）PBDEs、PCBs和NFRs暴露对成人性激素的干扰。NFRs和PBDEs对男性睾酮、女性促卵泡激素（FSH）的具有相似的干扰效应。PBDEs和NFRs的暴露及其交互作用导致暴露组女性的FSH浓度显著低于对照组。该结果有助于进一步研究PBDEs和NFRs暴露对性激素的干扰，并促使我们更加关注暴露所导致的健康风险。