苯并(a)芘暴露产活性氧介导海洋鱼类抗菌肽的表达机制及其在核转录因子信号通路中的作用

项目名称： 苯并(a)芘暴露产活性氧介导海洋鱼类抗菌肽的表达机制及其在核转录因子信号通路中的作用

项目编号： No.41276102

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 天文学、地球科学

项目作者： 王克坚

作者单位： 厦门大学

项目金额： 92万元

中文摘要： 传统认为苯并(a)芘（BaP）的免疫毒性效应可影响鱼类健康，但从机制上研究其毒性效应与免疫反应之间的关系少有报道。我们发现，细菌LPS刺激和BaP暴露都显著诱导鱼类抗菌肽hepcidin（Hepc）表达，LPS诱导表达与免疫功能相关，而BaP诱导Hepc高表达的生物学意义及表达调控的通路为何？值得深入研究。已报道污染物产生的活性氧（ROS）与核转录因子NF-κB参与的信号通路相关。本研究用模式生物海水青鱂和黑鲷，比较研究BaP暴露产生的ROS和NF-κB/STAT信号调节下Hepc的表达模式，及诱导的P450代谢反应与炎症因子的关系；以RNAi技术研究BaP暴露产生的ROS与NF-κB及Hepc mRNA表达的关系；从而阐明ROS诱导Hepc高表达的机制与信号通路。并研究了BaP暴露诱导Hepc高表达的生物学功能。该研究将从机制上揭示污染物毒性效应与免疫应答的相互关系，具有重要的科学意义。

中文关键词： hepcidin；LPS；BaP；NF-κB通路；ROS

英文摘要： The immunotoxic effect caused by benzo[a]pyrene (BaP) exposure is commonly believed to be harmful to fish health, but study in mechanism on interactions between this effect and the immune response of fish is little known. Our previous study found that the hepcidin gene from marine cultured fish is significantly induced either by LPS challenge or upon BaP exposure. As we know, LPS-induced hepcidin expression is involved in the immune function. So what is the biological function for high expression of hepcidin induced upon exposure to BaP? Which factor is involved in regulating the hepcidin expression during BaP exposure? These questions are worth elucidating. It has been reported that ROS generated during BaP exposure mediates the activation of the transcription factor NF-κB which is crucial in a series of cellular processes, thus possibly influencing NF-κB signalling pathway. To answer these questions, marine medaka and marine cultured black porgy will be used to carry out this study. The study includes: (1) To compare the hepcidin gene expression patterns regulated by ROS with the one via NF-κB/STAT; (2) To understand the correlation between CYP1A1 mediated reactions via AhR and the responses stimulated by inflammatory factors; (3) To clarify the relationships among the generation of ROS by BaP exposure, the NF

英文关键词： hepcidin；LPS；BaP；NF-κB pathway；ROS