六溴环十二烷及其复合污染脑发育期暴露对大鼠甲状腺激素代谢过程的影响

Disrupting Effects of Hexabromocyclododecane (HBCD) and its complex compounds on rat thyroid hormone metabolism after developmental exposure

研究六溴环十二烷(HBCD)及其复合污染对发育期幼鼠甲状腺激素代谢过程的影响。设计HBCD单一暴露剂量(10、50、100、300μg·kg-1),及HBCD与等浓度商用多溴联苯醚DE-71按2∶1复合暴露剂量(10、50、100、300μg·kg-1),对新生3 d的SD大鼠进行为期42 d的暴露,放射免疫法测定血清中甲状腺激素(TT3,TT4,FT3,FT4,TSH)水平,并分别测定肝脏和脑组织中甲状腺激素脱碘酶(D1,D2)活性及其对应基因的相对表达水平。与对照组相比较,经HBCD暴露后,大鼠血清中TT4、TT3、FT4、FT3浓度随着暴露剂量增大呈现先升高后下降的趋势,其中10μg·kg-1剂量组的FT3质量分数显著升高(P<0.05),300μg·kg-1剂量组的FT4质量分数显著下降(P<0.05);TSH则呈现下降趋势。10、50及300μg·kg-1剂量组的TSH质量分数均显著下降(P<0.05)。HBCD/DE-71复合暴露后,大鼠血清中TT4、TT3、FT4、FT3浓度随着暴露剂量的增大呈升高趋势,其中50μg·kg-1剂量组TT4质量分数显著升高(P<0.05),50μg·kg-1及300μg·kg-1剂量组FT4质量分数显著升高(P<0.05),300μg·kg-1剂量组FT3质量分数显著升高(P<0.05)。单一暴露后,D1活性及基因表达水平均呈下降趋势,300μg·kg-1剂量组基因表达水平下降显著(P<0.05);D2活性及基因表达水平则均呈现下降趋势,50μg·kg-1剂量组均显著下降(P<0.05);HBCD/DE-71复合暴露后,D1、D2活性及其基因表达水平则均呈升高趋势,其中100μg·kg-1剂量组D1活性及基因表达水平均显著性升高(P<0.05),300μg·kg-1剂量组D2活性显著性升高(P<0.05)。HBCD及HBCD/DE-71复合污染物均能通过改变甲状腺激素代谢酶的活性及mRNA表达水平进一步影响机体甲状腺激素的内稳态平衡,且HBCD单一暴露与HBCD/DE-71复合暴露对机体毒性作用途径及所产生的毒性效果存在着很大的差异。

To study the disrupting effects of Hexabromocyclododecane （HBCD） and its complex compounds on rat thyroid hormone metabolism after developmental exposure. Sprague-Dawley rats of 3-days old were exposed to different doses of HBCD （10, 50, 100, 300 Ixg＇kgl body weight） and HBCD/DE-71（10, 50, 100, 300μg·kg-1 body weight） for 42 days, Thyroid hormone levels in serum were detected using radioimmunoassay. Deiodinase I （D1） and Deiodinase II （D2） gene expressing levels were tested by Real-time fluorescence quantitative PCR assay and the enzyme activity of D1 and D2 were tested with Chopra＇s method. Compared with the controls, after HBCD exposure, serum TT4, TT3, FT4 and FT3 concentrations increased at first but then on a downward trend with increased exposure dosage; FT3 concentration of 10 μg·kg-1 exposures increased significantly （P〈0.05）; FT4 concentration of 300 μg·kg-1 exposures decreased significantly （P〈0.05）. There was a decline trend of TSH concentration at different exposure doses. TSH concentration of 10, 50 and 300 μg·kg-1 exposures all decreased significantly （P〈0.05）. After HBCD/DE-71 complex compounds exposure, there were increased trends of serum TT4, TT3, FT4 andFT3 concentration with increased exposure dosage; TT4 concentration of 50 μg·kg-1 exposures increased significantly （P〈0.05）; FT4 concentration of 50 μg·kg-1 and 300 μg·kg-1 exposures increased significantly （P〈0.05）; FT3 concentration of 300 μg·kg-1 exposures increased significantly （P〈0.05）. After HBCD exposure, D1 activity and its gene expression level both appeared to decline, and D1 gene expression level of 300 μg·kg-1 exposures decreased significantly （P〈0.05）. Also, D2 activity and its gene expression level both appeared to decline, and D2 activity and its gene expression level of 50μg·kg-1 exposures decreased significantly （P〈0.05）; After HBCD/DE-71 complex compounds exposure, enzyme activity and the gene expression of D1 and D2 were all increased. D1 activity and its gene expression level of 100 μg·kg-1 exposures increased significantly （P〈0.05）, and D2 activity of 100 μg·kg-1 exposures increased significantly （P〈0.05）. HBCD and HBCD/DE-71 complex compounds both altered the activities and gene expression levels of thyroid hormone metabolic enzymes. This process can be further influenced thyroid hormone homeostasis balance. There were great difference in toxic effect way and toxic effects for HBCD single exposure and HBCD/DE-71 complex compounds exposure.