【摘要】 缩节胺是一种食品热加工过程易产生的食品污染物，主要在特定的焙烤条件下形成。其生成途径是游离赖氨酸、还原糖和烷化剂进行美拉德反应。暴露于缩节胺可导致肾脏空泡化和肝、脾损伤，然而其在体内的代谢机制尚不清楚，这使得对缩节胺暴露风险的评估难度进一步加大。利用基于气相色谱-质谱联用的非靶向代谢组学方法研究缩节胺对大鼠尿液代谢物的影响，寻找差异代谢物，分析大鼠肾脏的组织病理学变化。研究结果表明，在缩节胺暴露前后的大鼠尿液中共筛选出24种差异代谢物，其中5种代谢物上调，19种代谢物下调。对差异代谢物进行代谢途径分析发现，暴露前后有5种代谢途径响应值大于0.1,是相对重要的被扰动代谢途径。它们分别为甘氨酸、丝氨酸和苏氨酸的代谢，甘油酯代谢，戊糖和葡萄糖醛酸的相互转化，磷酸肌醇代谢，乙醛酸和二羧酸代谢。这些代谢途径主要与氨基酸代谢、能量代谢、糖类代谢和脂质代谢相关。其中，响应值最大的代谢途径为甘氨酸、丝氨酸和苏氨酸的代谢。研究旨在为阐明缩节胺的毒性机制提供理论参考。更多还原

【Abstract】 Mepiquat(Mep) is a food contaminant produced usually during heat processing. It is formed by Maillard reaction with free lysine, reducing sugar and alkylating agent under typical roasting conditions. It was found that Mep exposure could cause kidney vacuolization, liver and spleen damage, but its metabolic mechanism in vivo was still not clear, which made it difficult to assess its exposure risk. Untargeted metabolomics was used to reveal effects of Mep on the metabolic profile of urine in rats based on gas chromatography-mass spectrometry. Differential metabolites and histopathological changes of rat kidneys were analyzed. The result showed that 24 differential metabolites were screened out from rat urine before and after Mep exposure. Among them, 5 metabolites were upregulated, 19 metabolites were down-regulated. Metabolic pathway analysis of the differential metabolites revealed that 5 major perturbed metabolic pathways were found with response values greater than 0.1 before and after the exposure of Mep, which were glycine, serine and threonine metabolism, glycerolipid metabolism, pentose and glucuronate interconversions, inositol phosphate metabolism, and glyoxylate and dicarboxylic acid metabolism. These pathways were mainly related to amino acid metabolism, energy metabolism, carbohydrate metabolism and lipid metabolism. Glycine, serine and threonine metabolism was the metabolic pathway with the largest response value. It was hoped that this study could provide theoretical reference for elucidating the toxic mechanism of Mep.更多还原