2,2＇,4,4＇-四溴联苯醚对小鼠甲状腺毒性作用  

Effects of 2,2',4,4'-tetra brominated diphenyl ethers(BDE-47) on thyroid hormone and cyp3a11 and cyp2b10 mRNA expression and their relationship in C57BL/6 mice

作　　者：刘早玲[1,2] 刘继文[2] 张建清[1] 田亚楠 方道奎[1] 黄海燕[1] 蒋友胜[1] 周健[1] 张红宇[1] 梅树江[1] 

机构地区：[1]深圳市疾病预防控制中心二嗯英实验室,518020 [2]新疆医科大学公共卫生学院劳动卫生与环境卫生学教研室 [3]美国德克萨斯州A&M大学

出　　处：《中国公共卫生》2010年第7期870-871,共2页Chinese Journal of Public Health

基　　金：国家自然科学基金(30771778)

摘　　要：目的探讨2,2',4,4'-四溴联苯醚(BDE-47)对小鼠甲状腺激素系统影响及其毒性机制。方法将C57BL/6小鼠分成阴性对照组、孕烯醇硐16α-睛(PCN)和1,4-双[2-(3,5-二氯吡啶氧)]苯(TCPOBOP)阳性对照组及低、中、高BDE-47染毒组,连续4d腹腔注射后,电化学发光免疫法测定小鼠血清总三碘甲状腺原氨酸(TT3)、四碘甲状腺原氨酸(TT4)和(TSH)促甲状腺激素,荧光定量法测定肝脏cyp2b10、cyp3a11和葡萄糖醛酸转移酶(UGT1A1)和硫酸基转移酶(SULT1A1)mRNA表达。结果与阴性对照组比较,染毒组小鼠血清TT4水平均降低(P<0.01),中、高剂量染毒组TT3水平降低(P<0.01);低、中、高染毒组小鼠肝脏cyp3a11mRNA表达分别为阴性对照的2.5,3.3,4.5倍(P<0.05),高剂量组cyp2b10mRNA表达水平上调是阴性对照的1.4倍(P<0.05);中、高染毒组小鼠肝脏UGT1A1和SULT1A1mRNA表达分别为阴性对照组的2.1,2.0倍(P<0.05)和1.7,2.0倍(P<0.05)。结论 BDE-47可以产生甲状腺激素干扰毒性,其分子机制可能与激活孕烷χ受体(PXR)和组成型雄甾烷受体(CAR),促使其靶基因UGT1A1和SULT1A1mRNA表达上调有关。Objective To investigate the effects of 2,2＇,4,4＇-tetrabrominated diphenyl ethers（BDE-47） on triiodothyronice（TT3）,total thyroxine（TT4）,thyroid-stimulating hormone（TSH）,and mRNA levels of cyp2b10,cyp3a11,UOP-gluceronosyltranse-ferase 1 family（UGT1A1） and sulfotransferase（SULT1A1） in the liver of C57BL /6 mice.Methods C57BL /6 mice were divided randomly into 6 groups and administrated with corn oil（negative control group）,50 mg /kg /day pregnenolone（16α-carbonitrile）（positive control group）,3 mg /kg /day 1,4 bis（2[3,5-dichloropyridyloxy]） benzene（positive control group）,0.5 mg /kg /day（low dose group）,5 mg /kg /day（medium dose group）,and 50 mg /kg /day（high dose group）BDE-47 for 4 days through intraperitoneal injection,respectively.The serum livels of T3,T4,and TSH were detected with electro-chemiluminescene（ECLI） and the mRNA levels of cyp2b10,cyp3a11,UGT1A1,and SULT1A1 in liver were detected with real-time PCR method.Results Compared with the control group,the levels of TT4 decreased significantly in all BDE-47 dose groups.TT3 in the medium and high dose BDF-47 groups decreased significantly（P 0.05）.The mRNA levels of cyp3all were up-regulated in the three BDE-47 dose groups.Up-regulation expression of cyp2b10 was observed only in the high dose BDF-47 group.On the other hand,the mRNA levels of UGT1A1 and SULT1A1 were up-regulated in the medium and high BDE-47 dose groups.Conclusion BDE-47 could affect the homeostasis of thyroid hormone system and the molecular mechanisms might be involved in its activation to pregnane X-receptor and constitutive androstane receptor and regulations for the mRNA expression of UGT1A1 and SULT1A1.

关 键 词：2 2' 4 4'-四溴联苯醚(BDE-47) 总三碘甲状腺原氨酸(TT3) 总四碘甲状腺原氨酸(TT4) 细胞色素P450 葡萄糖醛酸转移酶 

分 类 号：R587.1[医药卫生—内分泌]