抗抑郁类精神药物在典型城市水体中的污染特性及其生态风险分析

Due to the ineffective removal of pharmaceuticals by commonly used sewage treatment methods, in cities of America and some European countries it has been shown by previous studies that the concentrations of antidepressants and other psychotropic drugs in drinking water, municipal sewage, receiving river water, sediments and aquatic biological tissues are between ng to μ g/L or ng to μ g/kg. Since the effective concentrations of active ingredients of antidepressants are always significantly low, their sustained input to aquatic system should produce great impacts on the aquatic organisms and even on the whole aquatic environments and human health which makes them have become one of the concerned emerging contaminants in recent years. This project aims to characterize the pollution status of antidepressants in urban water system in Shanghai and especially to evaluate their adverse effects on fish species in aquatic ecosystem. The following goals will be achieved: to characterize the pollution levels, the source and distribution of antidepressants in the whole urban water system in Shanghai; to understand the indirect photolysis mechanism of antidepressants in water and obtain their toxicokinetic data during that process; to assess the adverse effects of antidepressants on oxidative stress, immune and neural systems in fish upon antidepressant exposure at environmental relevant concentrations; to explore the joint toxicity of their combined exposure, determine the toxicity thresholds and evaluate the ecological risk; and further, combining in vitro and in vivo experiments, to investigate their endocrine disrupting effects on the hypothalamic-pituitary-adrenal (HPA) axis of fish and clarify their action mechanism. The present project should provide better understanding of the characteristics and ecological risks of antidepressant pollution in urban water system in China. For protecting urban water resources and the healthy development of water environment it has important scientific significance.

抗抑郁类精神药物是近年来备受关注的新兴污染物，由于常用的污水处理方法对该类物质的去除几乎无效，在欧美国家城市的饮用水、污水以及河流受纳水体和水生生物中都能检测到其药物活性成分的存在，对水生生态系统和人类健康造成潜在的威胁。本项目以上海市为研究对象，开展抗抑郁类药物在我国典型城市水体中的污染特性研究，探明其污染水平、分布特征、分析其来源，掌握其在水体中的降解特征、机理和光解中间产物的毒性动力学；同时，开展环境相关浓度的抗抑郁药物暴露对鱼类的氧化压迫、神经毒性和免疫毒性研究，分析其联合暴露毒性，确定毒性效应阈值，评价其生态风险；并进一步从“垂体-下丘脑-肾上腺”轴入手，结合离体实验和在体实验，阐明抗抑郁药品低剂量长期暴露对鱼类的内分泌干扰效应及其作用机理。本项目将系统和深入的了解我国城市水体中抗抑郁类精神药物的污染特性及其生态风险，对于保障城市水质资源和水环境的健康发展具有重要的意义。

抗抑郁药的大量使用导致其可以通过多种途径进入城市水体，对水生生物产生毒性效应，并通过生物链传递，给生态系统和人体健康带来危害，相对于欧美国家而言，我国对于抗抑郁药水体污染的生态风险研究还很缺乏。本项目以上海市为研究对象，研究了该类药物在典型流域的分布特征及溯源，阐明了该类药物在典型城市水体系统的迁移转化规律，并以精神病医院作为点污染源的代表，重点分析了点源污染对周边环境的影响。研究发现，精神类药物在地表水、土壤及植物样品中均有检出，在医院污水出水中阿米替林（83.57 ng/L）、劳拉西泮（22.26 ng/L）有检出，这些数据揭示了这类精神药物在上海市不同介质中的空间分布格局，指出了不同区域污染状况与排放点源之间的关系。以筛选出的典型的抗抑郁类药物为代表，模拟了抗抑郁类药物的光照降解过程，结合电子束辐照降解机理，分析了目标物的降解中间产物，并研究了降解产物对水生生物的潜在毒性效应。研究发现，电子束辐照技术对舍曲林和西酞普兰的降解有非常好的效果，在不同浓度水平下，两种物质降解率分别可以达到99.7%和99.5%。通过HPLC-TOF-MS和离子色谱（IC）进一步表征了药物的降解中间体，确定了水溶液中舍曲林和西酞普兰分解的可能途径。在此基础上，对抗抑郁药可能引发的水体生态风险进行了研究，以斑马鱼作为水生生态风险评价的代表性物种，探明了抗抑郁类药物对水生生物发挥内分泌干扰作用的毒性机制。研究表明，环境浓度下的抗抑郁药可调节斑马鱼幼鱼大量基因的表达，对发育、生殖、神经及生理节律等产生负面效应；在长期和短期暴露后，抗抑郁药氟西汀可在幼年鱼不同组织中得到富集，可以推测鱼体内药物浓度是引起毒性效应的主要原因，上述研究结果为抗抑郁药的污染风险评估和风险管理提供了理论依据。通过以上研究，在国内外期刊上发表论文30多篇，其中SCI收录近30篇，培养博士生2名，硕士生6名。圆满完成了计划任务和预期目标。