纳米银在鱼鳃中的迁移转化和致毒机制

The migration, accumulation and toxic effects of nanomaterials in the ecological environment are the critical research topics in the recent years. However, the mechanism that involved in nanoparticles across the biological barriers from outside of aquatic environment into the organism inside is still unknown. Gill is a principal target organ for the nanomaterials of aquatic exposure, which often employed as an ideal organ model for exploring the transportation of nanomaterials across the biological barriers. Previous reports suggested that nanomaterials may across the gill epithelial through the cell membrane penetration, endocytosis and intercellular tight junctions to entry into the fish body, but the specific transport pathways and mechanism of transformation is unclear.In this study, the effect of physicochemical properties of silver nanoparticles (AgNPs) on its migration behaviors in gill surface will be investigated firstly. Then, the pathway of trans-membrane transportation of AgNPs, and its migration and transformation process within gill tissue will be further revealed. The mechanism involved in the toxic effect of AgNPs on the gill injury will be clarified during they get through the tissue barrier. This study has important implication for the mechanism of AgNPs getting cross the biological barriers. It also has important theoretical contribution to elucidating the toxic mechanism of AgNPs to organism and its behavior in the aquatic environment.

纳米材料在生态环境中的迁移、积累及毒性效应是污染生态化学研究的新热点，但纳米颗粒如何跨越生物屏障，从外界水环境进入到生物体内部的机制不明。鱼鳃是水环境纳米材料暴露的重要靶器官，也是研究纳米材料透过生物屏障的理想组织模型。前期研究提示，纳米材料可能通过鳃上皮细胞膜渗透、细胞内吞和细胞间紧密连接等途径跨越鱼鳃组织屏障而进入鱼体，但其具体的转运途径和转化机制尚不清楚。本研究拟以纳米银为代表，考察理化特性对纳米银在鱼鳃表面迁移行为的影响，揭示纳米银在穿越鱼鳃组织过程中的跨膜转运途径、组织内迁移和转化过程，明晰纳米银透过鱼鳃过程中的毒性效应及机制，阐明纳米银穿越鱼鳃组织屏障的机理。本研究对揭示纳米银跨越生物组织屏障的机制具有重要价值，对阐明纳米银水生态环境行为和致毒机制有重要理论意义。

纳米银在水生态环境中的迁移、积累和毒性效应是当前污染生态化学研究的热点。鱼鳃是水环境纳米颗粒暴露的重要靶器官，然而，纳米银颗粒如何跨越鱼鳃组织屏障并产生毒性效应的机制仍不清楚。本项目以鱼鳃为组织模型，主要开展了以下六各方面的工作：（1）采用暗场实时成像技术揭示了单颗粒纳米银在水体和鱼鳃中的动力学特性；（2）运用生物配体模型和生物富集动力学模型，揭示了不同粒径纳米银和银离子在鱼鳃中的积累和排出的动力学过程；（3）利用水生动物呼吸仪和组织病理学技术，揭示了AgNPs暴露引起的鲤鱼呼吸压力与鳃组织病理特征之间的相关关系。（4）研究了不同亚致死浓度的纳米银暴露96小时对鱼鳃膜的脂肪酸组成、膜的流动性、膜脂质过氧化和鳃的组织病理结构的影响，揭示了纳米银对鱼鳃膜损伤的毒性机制。（5）采用组织病理学和蛋白质组学的方法，揭示鲤鱼急性暴露于纳米银和硝酸银后，鱼鳃组织的形态和蛋白质组的变化状况以及可能的蛋白质调控机制。（6）通过整合转录组学和代谢组学技术，揭示了纳米银急性（24 h）暴露和7天恢复过程中鱼鳃的毒性响应机理，及损伤后恢复的可塑性机制。这些研究结果对揭示纳米银在水生态环境中的行为和致毒机制具有重要理论价值。