多种单端孢霉烯族毒素在动物体内体外的联合代谢研究

Trichothecenes are one of the most serious toxic mycotoxins which mainly contaminate food crops and feeds. Food safety issues caused by trichothecenes and their metabolites can bring great loss to husbandry as well as the direct and indirect threat to both animals and human beings. This project aims at three widespread and most toxic trichothecenes, including T-2 toxin, Deoxynivalenol (DON), and Nivalenol (NIV). To make the investigation more close to natural pollution, joint metabolism in rats of multiple trichothecenes was proposed. In the previous, reports of mycotoxin metabolism study mainly focused on single mycotoxin. This project will aim (1) to investigate the joint metabolism of multiple trichothecenes and obtain the information of metabolic toxin interactions both in vivo and in vitro; (2) to study the comparative metabolism between single and joint metabolism of trichothecenes. We believe that this work will illustrate the joint metabolism and elimination of multiple trichothecenes in animals, and make up for the inadequacy of single metabolism as well. Moreover, we also believe this work will contribute to the control of trichothecenes and provide basis for clinical treatment of poisoning.

单端孢霉烯族毒素是粮食和饲料中污染最为严重的真菌毒素之一，由毒素及其代谢产物所引起的食品安全问题不仅给农牧业造成了巨大的经济损失，也给人和动物的健康构成直接或潜在危害。本项目以污染广泛且毒性较强三种单端孢霉烯族毒素：T-2毒素、脱氧雪腐镰刀菌烯醇（DON）和雪腐镰刀菌烯醇（NIV）为研究对象，通过构建大鼠体外和体内联合代谢模型，对多种单端孢霉烯族在动物体内外的联合代谢过程进行探索。为了更真实的模拟自然条件，项目在传统的单一毒素代谢基础之上，提出了多种毒素联合代谢的研究方案，同时将毒素的联合代谢与单一代谢的结果进行比较代谢研究，进一步阐明毒素的联合代谢规律。项目的成功实施，将有助于利用联合代谢模型阐明单端孢霉烯族毒素在动物体内的联合代谢和消除规律，弥补毒素单一代谢研究的不足，从而有效地预防和控制毒素对人类和畜牧业的危害，并为毒素中毒后的治疗提供理论依据。

采用液相串联高分辨质谱技术系统开展了T-2毒素、DON和NIV在动物体内外的单个/联合代谢研究，阐明三种毒素的关键代谢途径、代谢产物、种属代谢差异和联合毒素代谢规律。体内外代谢研究中共识别和鉴定20余种T-2毒素的代谢产物，水解、羟基化、脱环氧、羧酸化和葡萄糖醛酸结合是其主要代谢产物，尽管T-2毒素存在显著的雌雄代谢差异和种属代谢差异，但是HT-2为其优势代谢产物。DON和NIV在体内外代谢试验中具有一定的代谢稳定性，分别发现了5种和2种代谢产物，葡萄糖醛酸化是两者优势代谢途径。联合毒素代谢研究结果表明三种毒素之间的相互影响非常有限，在毒素的代谢途径方面并无显著差异，仅仅是在代谢产物含量的方面存在一定差异，这表明三种毒素在大鼠体内的药物相互作用较小。