得克隆异构体在斑马鱼脑和肝脏中的生物应答及蛋白表达谱比较研究

Dechlorane Plus (DP), also known as a chlorinated flame retardant, is recently identified in the environment, with a high production volume. Recent studies have showed that DP can be disseminated by air and water, bioaccumulate in organisms and thus exist persistently. DP was introduced as a substitute for Mirex and Mirex has been banned because of its impact on the environment. However, toxicity data for DP are rare. There is an urgent need for more researches on DP toxicity and biological mechanism to give more objective toxicological evaluations on this fast-growing flame retardant. Evidence now exists that DP readily accumulates within fishes and the distributions of syn- and anti-DP are different in liver and brain, which suggests the toxicological and metabolic mechanisms of syn- and anti-DP may be different. Our previous research demonstrates that DP exposure can induce superoxide dismutase (SOD) activity increasing, cell apoptosis in intestine and gene expression changing in zebrafish. In this study, according to the different distributions of syn- and anti-DP, comparative study of DP isomers on oxidative stress responses, cell apoptosis and proteomic expression profiles in zebrafish liver and brain will be carried out. Results obtained in this study will provide clue to the possible mechanisms on toxic effects and metabolism of DP isomers in zebrafish liver and brain, and thus provide evidences for toxicity evaluation of DP to aquatic animals. Moreover, target proteins obtained from proteomic study can be used as biomarkers in further studies on DP toxicological and metabolic mechanisms and toxicity evaluation.

得克隆（Dechlorane Plus, DP）作为一种在环境中持久存在、具生物富集性、以空气和水为传播介质、使用量巨大的氯代阻燃剂，其毒理学研究非常有限，急需对DP的毒理效应及作用机制进行深入研究。已有研究表明，DP可在鱼类脑和肝脏中蓄积，且顺反异构体的分配不同，推测顺式（syn-）和反式（anti-）DP在生物体内可能存在不同的代谢方式和毒性作用机制。我们的前期研究表明DP暴露可引起斑马鱼（Danio rerio）超氧化物歧化酶（SOD）活性的改变、细胞凋亡及基因表达水平的改变。本研究针对DP在脑和肝脏中不同的蓄积方式，拟从氧化应激、细胞凋亡和蛋白质组表达层面，比较syn-和anti-DP在斑马鱼脑和肝脏中生物应答和作用机制的异同，为客观评价DP的生态风险提供理论依据；另外，蛋白质组分析获得的靶蛋白可作为分子标志物，用于后续DP毒性作用机制、代谢调控和毒性诊断研究中。

得克隆（Dechlorane Plus, DP）作为一种在环境中持久存在、具生物富集性、以空气和水为传播介质、使用量巨大的氯代阻燃剂，其毒理学研究非常有限，目前缺乏DP对淡水鱼类的毒性效应研究。本研究采用斑马鱼为受试生物，针对DP在脑和肝脏中不同的蓄积方式，从氧化应激、细胞凋亡和蛋白质组表达层面，比较DP在斑马鱼脑和肝脏中生物应答和作用机制。结果表明DP暴露7天后，脑和肝脏积累的DP含量、fsyn值和BCF各不相同，syn-DP更容易富集于脑组织。DP亚急性暴露处理后的斑马鱼肝、脑组织的SOD、CAT酶活性，均表现出明显的浓度-效应关系和时间-效应关系，但脑组织对DP的响应和修复更为敏感。7.5 mg DP/g bw暴露处理28天，在脑和肝脏均发生明显的细胞凋亡现象。蛋白质组分析表明，DP暴露后斑马鱼脑和肝脏的蛋白表达谱完全不同，脑中差异表达的蛋白点主要与神经毒性和神经保护相关，而肝脏中差异表达的蛋白点主要与DNA损伤、蛋白质合成、免疫应答和细胞凋亡相关。本课题的研究为客观评价DP的生态风险提供了理论依据，蛋白质组分析获得的靶蛋白可作为分子标志物，用于后续DP毒性作用机制、代谢调控和毒性诊断研究中。