抗生素在紫贻贝体内的生物富集和毒代动力学机制研究

沉积物是抗生素在环境中重要的汇，也是底栖动物的潜在暴露源。目前，抗生素在底栖无脊椎动物体内富集和毒代动力学机制仍不清楚，尤其是对其沉积物吸附态肠道吸收和体内代谢机制知之甚少。本项目以一种重要的海产品和海洋污染指示物种——紫贻贝(Mytilus edulis)为受试生物，采用动物活体实验结合离体实验研究抗生素在其体内的生物富集和毒代动力学，重点探究其肠道吸收和体内代谢机制。通过半静态暴露实验和一级动力学单室模型比较人工海水和人工海水-沉积物两种暴露场景中紫贻贝对抗生素的差异性富集行为；利用离体肠道灌流技术研究沉积物吸附态抗生素在紫贻贝肠道中的吸收动力学、机制及影响因素；运用非靶向筛查、体外代谢酶抑制实验和串联/高分辨质谱等手段，研究抗生素代谢产物、代谢途径及动力学特征。研究结果可为利用紫贻贝指示近海环境抗生素污染及海洋贝类的健康风险评估提供科学依据。

Sediments represent one of the important sinks of antibiotics in the environment, also are potential sources of antibiotic exposure to benthic organisms. However, the bioaccumulation and toxicokinetics of antibiotics in marine benthic invertebrates remain unknown, especially for the intestinal absorption of sediment-bound antibiotics and the metabolism mechanism. Blue mussel (Mytilus edulis) is a commercially important seafood and a widely-used indicator of marine pollutants. In this project, blue mussel will be used as the test organism and the bioaccumulation and toxicokinetics of selected antibiotics will be explored by combining in vivo and in vitro experiments. The underlying mechanisms of intestinal absorption and metabolism will be emphasized. Firstly, the different bioaccumulation behaviors of antibiotics in two exposure scenarios, i.e. artificial seawater only and artificial seawater-sediment particles, will be compared using a series of semi-static bioaccumulation experiments and a first-order one-compartment model; Secondly, the absorption kinetics and absorption mechanism of sediment-bound antibiotics and the main influence factors will be investigated in isolated intestinal tract by perfused chamber technique; Thirdly, the metabolites, metabolic pathways and kinetics of antibiotics will be analyzed by in vivo non-target screening, in vitro inhibition of metabolic enzymes, and tandem/high-resolution mass spectrometry. The results from this project could provide scientific basis for monitoring of antibiotic contamination in coastal environment using blue mussel and health risk assessment of marine shellfishes.