环境激素三苯基锡（TPT）对鲤鱼生长干扰效应和机制研究

Global attention has been paid to TPT，which is typical endocrine disruptors. As a contaminant with wide distribution in aquatic environment of our country, the interference effects and mechanism of TPT on growth of fish is still unclear. Therefore, it is important to study the effects of TPT on growth of fish. In the present study, attentions are focus on the effects of TPT on growth hormone/ insulin-like growth factor 1 (GH/IGF-I) axis. Common carp (Cyprinus carpio) at different development stages and with different gender are used to elucidate the interference mechanism of low-dose TPT chloride on growth by physiological-biochemical methods and molecular approaches. Also, biomarkers reflect interference effects are screened in this study. Recombinant antibody against biomarkers are developed by phage display technology and used to evaluate the interference effects caused by TPT. The aims of this study are: (1) to identify toxicant-specific genes affected by TPT exposure; (2) to elucidate the interference mechanism of TPT on growth at molecular level; （3）to provide important information for ecotoxicology and environmental risk assessments.

三苯基锡（TPT）是典型的内分泌干扰物，并引起全球的关注。TPT广泛分布于我国水环境中，其对鱼类生长干扰效应及机制并不清楚。因此，研究TPT对鱼类生长的影响具有重大意义。本研究重点关注TPT对生长激素/胰岛素样生长因子（GH/IGF-I）轴的影响，以鲤鱼作为实验材料，以氯化三苯基锡为研究对象，通过生理生化和分子生物学等技术手段，从营养和内分泌两个方面初步探讨了低剂量TPT对不同发育阶段不同性别鲤鱼生长干扰的作用机制，并筛选反映TPT生长干扰效应的生物标志物，利用噬菌体展示技术制备重组抗体应用于评估TPT的生长干扰作用。通过本项目研究，可望发现TPT暴露条件下与生长相关的毒理效应基因；在分子水平上阐明TPT对鲤鱼的潜在生长干扰作用机制，为TPT的生态毒理及环境健康评价提供基础数据和理论依据。

三苯基锡（TPT）是典型的内分泌干扰物，并引起全球的关注。TPT广泛分于我国水环境中，其对鱼类生长干扰效应及机制并不清楚。因此，研究TPT对鱼类生长的影响具有重大意义。本项目研究了不同浓度TPT对不同发育阶段不同性别鲤鱼生长的影响，并从GH/IGF-1生长轴中关键因子的合成与分泌等方面探讨了TPT对鱼类生长干扰的机理。. TPT对鲤鱼幼鱼的96小时半致死浓度为24 ug/L。TPT抑制了鲤鱼的胰蛋白酶和脂肪酶的活性，影响营养物质消化与吸收，间接对生长产生影响；TPT抑制了GHR、IGFR、IGFBP的表达，降低IGF-1合成与转运，从而抑制鱼类的生长；IGF-1的减少，使GHRH、GHRHR、Ghrelin、NPY等表达量发生变化，影响GH的含量，影响鱼类的生长。筛选到IGF-1为反映TPT生长干扰效应的灵敏生物标志物，成功利用噬菌体展示技术制备IGF-1重组抗体。本研究初步弄清了TPT影响鱼类生长的作用机理，为TPT的生态毒理及环境健康评价提供基础数据和理论依据。