有机磷酸酯对斑马鱼的早期神经毒性作用研究

Neurotoxicity of Organophosphate Esters on the Early Life Stages of Zebrafish

国内外研究已证实,有机磷酸酯广泛分布于多种环境介质中,但目前仍缺乏足够的数据阐明有机磷酸酯具有早期神经毒性效应及其可能的毒性作用机制。本研究采用模式动物斑马鱼(Danio rerio)作为研究对象,选择了环境中3种典型的有机磷酸酯类化合物包括磷酸三苯酯(TPP)、2-乙基己基二苯基磷酸酯(EHDPP)和磷酸三(2-氯)乙酯(TCEP),从斑马鱼运动行为、氧化应激和神经发育关键基因的转录等方面阐述有机磷酸酯的早期神经毒性作用及可能的作用机制。研究发现,TPP(0.1和1 mg·L^-1)、EHDPP(0.2和2 mg·L^-1)和TCEP(0.5和5 mg·L^-1)可能通过诱导氧化应激并下调神经发育关键基因(mbp和syn2a)的转录从而显著抑制斑马鱼的运动行为。本研究可以为有机磷酸酯类阻燃剂及其替代产品的生产、使用和危险度评估提供直接依据。

Domestic and foreign studies have confirmed that organophosphates are widely distributed in a variety of environmental media but there is still lack of sufficient data to illustrate the early neurotoxic effect of organophosphate esters and its possible toxic mechanism.In this study,zebrafish(Danio rerio)was used as a model animal,and three typical organophosphate compounds,i.e.triphenylphosphate(TPP),2-ethylhexyl diphenyl phosphate(EHDPP)and tris(2-chloroethyl)phosphate(TCEP),were selected.The early neurotoxicity and possible mechanism of organophosphate in zebrafish were illustrated from the aspects of locomotor behavior of zebrafish,as well as its oxidative stress and expression of key genes for nerve development.It was found that,TPP(0.1 and 1 mg·L^-1),EHDPP(0.2 and 2 mg·L^-1)and TCEP(0.5 and 5 mg·L^-1)could significantly inhibit the locomotor behavior of zebrafish by inducing oxidative stress and down-regulating the expression of key genes for nerve development(mbp and syn2a).The research results of this study can provide direct scientific evidence for the production,using and risk assessment of organophosphate flame retardant and its substitute products.