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

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.

Thyroid hormone disrupting effects of organophosphorus flame retardants and its mechanisms of action,take TCPP as an example

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.