有机磷阻燃剂甲状腺干扰效应及其作用机制研究——以磷酸三(2-氯丙基)酯(TCPP)为例

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摘要以典型有机磷阻燃剂磷酸三（2-氯丙基）酯（TCPP）为研究对象，应用GH3细胞增殖实验检测TCPP对甲状腺激素的干扰效应；应用重组甲状腺激素受体（TR）基因酵母实验和GH3（TRβ-）细胞增殖实验结合实时定量PCR技术初步探究TCPP甲状腺激素干扰作用机理.结果表明，TCPP在1×10^-4mol/L和2×10^-4mol/L浓度下对甲状腺激素T3诱导的GH3细胞增殖产生抑制效应；重组TR基因酵母实验和GH3（TRβ-）细胞增殖实验测试结果表明TCPP可能通过TR介导的基因组途径和非基因组途径诱导甲状腺激素干扰效应；实时定量PCR测试结果表明TCPP下调相关基因如：c-fos、TRβ、integrin-av和k-ras的mRNA表达，初步认为TCPP可能通过影响TRβ基因表达和激活α_vβ₃-ERK-1/2信号通路产生甲状腺激素干扰效应.

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	沈扬
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关键词 ：有机磷阻燃剂, 甲状腺激素干扰效应, 作用机制, 甲状腺激素受体

Abstract：In the present study, typical organophosphorus flame retardants (OPFRs), tris (2-chloropropyl) phosphate (TCPP), was selected as the object of study. GH3 cell proliferation assay was used to test the thyroid disrupting activity of TCPP; a two-hybrid thyroid receptor (TR) yeast assay, GH3 (TRβ-) cell proliferation assay and real time quantitative PCR were used to investigate the mechanism of action. The results revealed that TCPP decreased the GH3 cell proliferation at concentrations ranging from 1×10^-4mol/L to 2×10^-4mol/L. Furthermore, the results from two-hybrid TR yeast assay and GH3(TRβ-) cell proliferation assay suggested that TCPP could disrupt thyroid hormone activity through genomic and non-genomic pathway. The results of real time quantitative PCR supported the mRNA expression levels of c-fos, TRβ, integrin-av and k-ras were inhibited, suggesting that TCPP might induce thyroid hormone disruption by adjusting TRβ gene expression and activating α_vβ₃-ERK-1/2 signaling pathway. All of these results could provide the basic data and theoretical support for the environmental risk assessment of TCPP.

Key words： organophosphorus flame retardants (OPFRs) thyroid hormone disrupting effects mechanisms of action thyroid receptor

收稿日期: 2017-10-23

171.5

基金资助:国家水体污染控制与治理科技重大专项资助项目（2014ZX07201-010）

作者简介: 沈扬(1993-),女,陕西延安人,北京师范大学硕士研究生,主要研究方向为环境毒理学.

引用本文:

沈扬, 于畅, 孔东东, 王荣芳, 李剑. 有机磷阻燃剂甲状腺干扰效应及其作用机制研究——以磷酸三(2-氯丙基)酯(TCPP)为例[J]. 中国环境科学, 2018, 38(6): 2337-2344. SHEN Yang, YU Chang, KONG Dong-dong, WANG Rong-fang, LI Jian. Thyroid hormone disrupting effects of organophosphorus flame retardants and its mechanisms of action, take TCPP as an example. CHINA ENVIRONMENTAL SCIENCECE, 2018, 38(6): 2337-2344.

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http://www.zghjkx.com.cn/CN/ 或 http://www.zghjkx.com.cn/CN/Y2018/V38/I6/2337

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