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刘早玲, 刘继文, 张建清, 田亚楠, 方道奎, 黄海燕, 蒋友胜, 周健, 张红宇, 梅树江. 2, 2’, 4, 4’-四溴联苯醚对小鼠甲状腺毒性作用[J]. 中国公共卫生, 2010, 26(7): 870-871. DOI: 10.11847/zgggws2010-26-07-35
引用本文: 刘早玲, 刘继文, 张建清, 田亚楠, 方道奎, 黄海燕, 蒋友胜, 周健, 张红宇, 梅树江. 2, 2’, 4, 4’-四溴联苯醚对小鼠甲状腺毒性作用[J]. 中国公共卫生, 2010, 26(7): 870-871. DOI: 10.11847/zgggws2010-26-07-35
LIU Zao-ling, LIU Ji-wen, ZHANG Jian-qing, . 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[J]. Chinese Journal of Public Health, 2010, 26(7): 870-871. DOI: 10.11847/zgggws2010-26-07-35
Citation: LIU Zao-ling, LIU Ji-wen, ZHANG Jian-qing, . 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[J]. Chinese Journal of Public Health, 2010, 26(7): 870-871. DOI: 10.11847/zgggws2010-26-07-35

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

  • 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。

     

    Abstract: ObjectiveTo 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.MethodsC57BL/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(23,5-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.ResultsCompared 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.ConclusionBDE-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.

     

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