六溴环十二烷转甲状腺素蛋白结合活性及其发育期暴露的甲状腺激素干扰效应研究

Transthyretin-binding Activity of Hexabromocyclododecanes (HBCDs) and Its Thyroid Hormone Disrupting Effects After Developmental Exposure

为了探讨新型溴代阻燃剂六溴环十二烷(HBCDs)的潜在健康危害,采用体外研究与动物暴露实验相结合的方法,分析了HBCDs与转甲状腺素蛋白(TTR)的结合活性,以及不同剂量HBCDs暴露对发育期大鼠体内甲状腺激素水平的干扰作用.TTR竞争结合实验显示,HBCDs与125 I-T4竞争结合TTR的能力随溶液浓度的增加而升高,但即使在80μmol.L-1的高浓度下,125I-T4与TTR的结合率仍高达75.08%,表明HBCDs抑制甲状腺激素T4与转运蛋白结合的能力较弱.动物实验结果表明,新生3 d大鼠暴露于0.2 mg/kg及1 mg/kg剂量的HBCDs 21 d后,与对照组相比,暴露组大鼠血清中总三碘甲状腺原氨酸TT3、游离三碘甲状腺原氨酸FT3的含量显著升高(p<0.05、p<0.05);总甲状腺激素TT4、游离甲状腺激素FT4含量下降约20%,促甲状腺激素水平上升30%～230%,但3个指标变化均不具统计学意义.结合体内实验及动物实验结果,HBCDs可能通过对甲状腺激素T3的协同或替代作用产生直接和间接的甲状腺干扰效应.低剂量的HBCDs暴露即可导致发育期大鼠甲状腺激素内稳态失衡,对HBCDs发育期暴露的毒性作用值得关注.

In vivo and in vitro research approaches were carried out to survey the potential health risk of environmental exposure by hexabromocyclododecanes（HBCDs）.Transthyretin-binding assay was designed to test for the potency of HBCDs to compete with thyroxine（T4） for binding to the transport protein.The results showed that the binding of 125I-T4 and T4 was only slightly inhabited even at the highest competitive concentration of HBCDs（75.08%,80μmol.L-1）,indicating the marginally interfere potency of HBCDs in the transportation of T4.Sprague-Dawley rats of 3-days old were exposed to 0.2mg /kg and 1mg /kg HBCDs for 21 d to examine the thyroid hormones（THs） disrupting effects of HBCDs after developmental exposure.Compared with the controls,levels of total 3,3′,5-triiodothyronine（TT3）,free 3,3′,5-triiodothyronine（FT3）,increased significantly（p 0.05,p 0.05） in low-and high-dose exposures,thyroid stimulating hormone（TSH） also increased slightly while the total thyroxine（TT4）,free thyroxine（FT4） had a decline about two-fold inversely.Combined both the in vivo and in vitro results,the possible mode of action of HBCDs on THs disruption may through the synergy or substitution effect of T3.The findings support further investigation of the potential THs disrupting effects of HBCDs on public health,especially on children during brain development.