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陈玫宏 1,2,徐怀洲1,宋宁慧1,张芹1,张圣虎1,*,李江2,#. 羟基多溴联苯醚(OH-PBDEs)小鼠肝脏微粒体体外代谢及对雌激素代谢的影响研究[J]. 生态毒理学报, 2018, 13(6): 136-143
羟基多溴联苯醚(OH-PBDEs)小鼠肝脏微粒体体外代谢及对雌激素代谢的影响研究
In vitro Metabolism of Hydroxyl Polybrominated Diphenyl Ethers (OH-PBDEs)and Effects on Estrogen MetabolisminMouse Liver Microsomes
投稿时间:2018-01-21  修订日期:2018-03-27
DOI:
中文关键词:  OH-PBDEs  肝脏微粒体  体外代谢  雌激素
英文关键词:OH-PBDEs  liver microsomes  in vitro metabolism  estrogen
基金项目:国家自然科学基金(No. 21407055, 51508120);
作者单位
陈玫宏 1,2,徐怀洲1,宋宁慧1,张芹1,张圣虎1,*,李江2,# 1. 生态环境部南京环境科学研究所南京 210042 2. 贵州大学资源与环境工程学院贵阳 550025 
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中文摘要:
      羟基化多溴联苯醚(OH-PBDEs)是一类具有内分泌干扰效应的酚类化合物,以小鼠肝脏微粒体作为研究对象,考察了OH-PBDEs的体外代谢行为及对雌激素代谢的影响。研究结果发现,4种OH-PBDE均能够代谢,其代谢率大小为6-OH-BDE-99>6’-OH-BDE-99>6-OH-BDE-137>5’-OH-BDE-99,表明羟基官能团(-OH)与醚键及溴原子处于邻位时,表现出较高的代谢率;4种OH-PBDE对3种天然雌激素包括雌酮(E1)、17β-雌二醇(E2)、雌三醇(E3)的代谢表现出不同作用,整体来说,对E1和E2代谢随着OH-PBDE浓度的增加抑制作用逐渐增强,对E3代谢则表现出促进作用,但是对人工合成的雌激素17α-炔雌醇(EE2)无明显影响;对E2代谢产物2-羟基雌二醇(2-OH-E2)的生成量定量表征表明,除6-OH-BDE-99促进了2-OH-E2的生成量,其余3种OH-PBDE随实验添加浓度的增加,抑制了2-OH-E2的生成量,这可能与酶介导的不同代谢机制有关。
  
AuthorAffiliation
Chen Meihong1,2, Xu Huaizhou1, Song Ninghui1, Zhang Qin1, Zhang Shenghu1,*, Li Jiang2,#1. Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China 2. College of Resources and Environmental Engineering, Guizhou University, Guiyang 550025, China
英文摘要:
      Hydroxylation polybrominated diphenyl ethers (OH-PBDEs) are a class of phenolic compounds that have been found to be an endocrine disruptor, and the in vitro metabolism of OH-PBDEs and effect on metabolism of synthetic estrogen were investigated using mouse liver microsome. The results showed that all of the four OH-PBDEs can be metabolized, and the metabolic rate followed the order: 6-OH-BDE-99>6’-OH-BDE-99>6-OH-BDE-137>5’-OH-BDE-99, which indicated OH-PBDEs were more readily bio-transformed when the hydroxyl functional group (-OH) was in the ortho position with the ether bond and the Br atom. The four OH-PBDEs showed different effects on the metabolism of natural estrogens, including estrone (E1), 17β-estradiol (E2), estriol (E3). As a whole, the inhibition on metabolic rate of E1 and E2 gradually increased with the increasing concentrations of OH-PBDE, but showed a promotion effect on metabolism of E3 and no significant effect on metabolism of synthetic estrogen 17α-ethynylestradiol (EE2). The quantification of the metabolite 2-hydroxyestradiol (2-OH-E2) showed that 6-OH-BDE-99 promoted the 2-OH-E2 production, while 2-OH-E2 production was inhibited by the other three OH-PBDEs as the experimental concentration increased, and these results revealed that it may be related to the different metabolic mechanisms mediated by enzymes.
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