随着社会经济的发展，人类排放的化学污染物种类和数量日益增多，给生态环境和人体健康造成了巨大威胁。为此，有必要对环境中的化学污染物进行毒性机理研究，以便于进行生物防治。ATP结合膜转运蛋白(ATP Binding Cassette Transporters，ABC转运蛋白)介导的转运过程是生物排泄外源物的主要途径之一，也是药物毒理学的重要研究内容。本项目旨在采用斑马鱼作为模式生物，进一步考察Mdr1、Mrps等主要ABC转运蛋白在化学污染物抵御中的作用。为此，我们拟检测不同发育阶段的斑马鱼中转运蛋白的表达情况，并筛选毒性与转运蛋白相关的化学污染物；之后分别从蛋白（表面等离子共振，SPR）、细胞（转染转运蛋白的细胞株）及体内（基因缺陷型斑马鱼）三个层次考察各转运蛋白与化学污染物的转运关系；最终检测化学污染物对ABC转运蛋白的诱导和抑制作用，探索转运蛋白在化学污染物联合毒性中的作用。

With the development of economy and city of our country, more and more chemicals are let out, which are harmful to the environment and human health. Therefore, a full investigation of the toxic mechanism of these chemicals is needed for the biological control of environment pollutions. Recent evidence indicates that ABC (ATP binding cassette) protein family recognized a wide variety of potential xenobiotic as substrates, pumping them out of the cell in an energy dependent, ATP driven process, and thus is considered to be important in drug toxicology investigation. This project aims to investigate the possible role of ABC transporters in the biological defense against environmental toxicants, using zebrafish as a model animal. In this respect, we would firstly detect the expression profile of ABC transporters during the development of zebrafish, and select the possible substrate of ABC transporters. Secondly, the role of ABC transporters in pumping out individual chemical pollutants would be examined by protein (surface plasmon resonance, SPR), cell (gene-cloned cell line), mRNA-silenced zebrafish. Finally, the induction and inhibition of ABC transporters by chemical pollutants would be detected to illustrate the mechanism of ABC transporter-mediated chemical interactions.