基于细胞代谢组学的农产品中单端孢霉烯族类毒素联合毒性评价及机制研究

Mycotoxin contamination has always been the difficulty and the focal point of the agricultural products quality and safety supervision. Trichothecenes is a class of mycotoxins with the highest global contamination rate whose combined toxic effects and mechanisms of its mixed contamination have not yet been clarified. This project was based on our previous study of typical mycotoxins combined toxicity on mice metabolome. (1) As the target cells of trichothecenes, Caco-2 and RAW 264.7 will be used as the cell mode to screen the combined toxicity assessment model under complex dose combinations of trichothecenes. (2) The trichothecene combined toxicity type will be calculated for studying the relationship between the toxicity type and cell lines, exposure time, and molecular configuration of trichothecenes. (3) Taking the level of cellular acetyl amino acid metabolism as the starting point, the mechanism of combined toxicity of trichothecene mycotoxin will be deeply clarified, combined with the expression level of cell metabolism pathway, key synthetases and regulatory genes. Similar research ideas have found wide innovative applications both at home and abroad. This project provides a theoretical basis and method for the study of the combined toxicity mechanism of mycotoxins. It has important theoretical and practical significance for risk assessment and prevention as well as the control of mycotoxins in agricultural products.

真菌毒素混合污染一直是农产品质量安全监管的难点与重点。单端孢霉烯族类毒素作为全球污染率最大的一类毒素，其混合污染产生的联合毒性效应及作用机制尚未明确。本项目在前期开展的典型真菌毒素在小鼠代谢组联合毒性研究的基础上：（1）以单端孢霉烯族毒素靶细胞Caco-2和RAW 264.7为细胞模型，明确单端孢霉烯族毒素复杂剂量组合下的联合毒性作用评价模型；（2）揭示联合毒性作用类型与单端孢霉烯族毒素分子构型的关系，阐述在不同细胞系不同时间内产生联合毒性类型的差异；（3）以细胞乙酰氨基酸代谢水平为切入点，结合细胞代谢通路、关键合成酶和调控基因的表达水平，阐明单端孢霉烯族毒素的联合毒性作用机制。类似研究思路在国内外均具有较好的创新性，项目开展为真菌毒素的联合毒性机制研究提供理论依据和方法借鉴，对农产品中真菌毒素风险评估和防控均具有重要的理论和实践意义。