磷酸三(2,3-二氯丙基)酯暴露诱发NRK-52E细胞纤维化的体外研究

Tris( 1,3-dichloro-2-propyl) Phosphate Induces NRK-52E Cells Fibrosis in vitro

自2004年禁止使用五溴联苯醚混合物阻燃剂以来,有机磷阻燃剂(organophosphorus flame retardants,OPFR)作为替代品开始被广泛生产和使用,因而成为当今阻燃剂研究的热点。目前,有机磷阻燃剂在水体环境及生物体中已有较高的检出率,而其对生物体及生态环境的潜在毒性效应还知之甚少。本研究利用磷酸三(2,3-二氯丙基)酯(tri(2,3-dichloropropyl)phosphate,TDCPP)对大鼠肾小管上皮细胞(NRK-52E)的毒性暴露实验,探讨TDCPP潜在的肾脏毒性。结果表明:一定剂量的TDCPP对NRK-52E的细胞活性有抑制作用,能诱导细胞内活性氧自由基(reactive oxide species,ROS)生成量增加,并触发上皮-间充质转换(epithelial-mesenchymal transition,EMT)及胞外基质沉积因子如波形蛋白(vimentin)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、胞外基质成分纤连蛋白-1(fibronectin-1,FN-1)等基因mRNA表达的显著上调以及上皮细胞钙粘蛋白(E-cadherin)等基因mRNA表达的显著下调。上述研究结果表明,TDCPP可促进NRK-52E细胞发生上皮间充质转化及纤维化。本研究为进一步综合评估TDCPP的生物和环境毒理效应提供了基础实验数据。

Since the prohibition of the commercialized pentabromodiphenyl ether compound fire retardants in 2004,organic phosphorus flame retardants（ OPFRs） have been produced and applied comprehensively as the substitute.Recently,the detectable rate of OPFRs in water environment and organisms is quite high,but studies about the potential adverse effect of OPFRs on organisms and thus ecosystems are scarce. The aim of the present study was toexamine the possible toxic effect of tris（ 1,3-dichloro-2-propyl） phosphate（ TDCPP） as a model OPFR substance.NRK-52 E cells were exposed to TDCPP,cell viability and extracellular matrix gene expression levels were measured. The results showed that the viability of NRK-52 E cells was significantly inhibited by TDCPP in both a dosedependent and time-dependent manner. TDCPP augmented the reactive oxygen species production in NRK-52 E cells. The expression of vimentin,transforming growth factor-β1（ TGF-β1） and fibronectin-1 was significantly upregulated,while E-cadherin was significantly down-regulated by TDCPP. In conclusion,TDCPP may have the ability to promote epithelial-mesenchymal transition and fibrosis in NRK-52 E cells. The result forms the foundation for future comprehensive evaluation of TDCPP toxic effects on the environment.