婴幼儿热加工食品中2-甲基呋喃形成及其诱导肝毒性的代谢机理研究

2-methyl furan which widely existed in heat processed food has been highly concerned because of its high level in baby foods. It has potential hepatotoxicity. However, its mechanism on formation and metabolism of inducing hepatotoxicity has not been clear. The relations among the precursors, possible intermediates and end-products from linolenic and linoleic acid model systems are investigated by advanced analytical methods. Meanwhile, the impacts of processing conditions and ways on 2-methyl furan formation are studied in order to speculate it’s the possible mechanism of formation. Furthermore, metabolomic is employed to analyze differences of metabolites in liver and blood of mice. Potential biomarkers and key metabolic pathways will be found. Molecular target will be clear. In order to reveal asymmetric spatial distribution of lipid metabolites from liver of mice, mass spectrometry imaging of mice is completed with MALDI-MSI and lipidomics. As a result, metabolic mechanism of 2-methyl furan in inducing hepatotoxicity will be clarified. In short, the project will provide theoretical basis for technology of safety control of 2-methyl furan, scientific basis for safe assessment and limited standard of 2-methyl furan in baby foods in China.

2-甲基呋喃是热加工食品中普遍存在的危害物，有潜在肝毒性，因其在婴幼儿食品中的高含量而备受关注，目前对其形成及诱导肝毒性的代谢机理仍不清楚。因此，本项目拟建立多不饱和脂肪酸模型体系，分析模型体系中前体物、可能中间物和终产物2-甲基呋喃之间的转化关系，考察热加工条件、热加工方式对模型体系中2-甲基呋喃形成的影响，阐明多不饱和脂肪酸形成2-甲基呋喃的机理。利用代谢组学高通量方法分析2-甲基呋喃暴露下小鼠肝组织的代谢物轮廓，寻找潜在的生物标记物与关键的代谢通路，揭示其作用分子靶点；利用质谱成像和脂质组学结合的方法对小鼠肝脏进行高灵敏质谱分子成像分析，进一步明确2-甲基呋喃暴露致小鼠肝脏脂质代谢紊乱和不对称空间分布，阐明其诱导肝毒性的代谢机理。本项目的实施，将为食品热加工过程中2-甲基呋喃的安全控制技术奠定理论基础，为2-甲基呋喃在热加工食品中暴露的安全性评价及其限量标准的制定提供科学依据。

2-甲基呋喃是热加工食品中普遍存在的危害物，有潜在肝毒性，因其在婴幼儿食品中的高含量而备受关注，目前对其诱导肝毒性的代谢机理仍不清楚。因此，利用非靶向代谢组学方法分析2-甲基呋喃暴露下小鼠肝脏、血液、尿液和脂肪代谢物轮廓，发现2-甲基呋喃诱导小鼠体内氨基酸、脂肪酸和糖代谢等代谢通路的紊乱，产生氧化应激，引起肝肾损伤。通过病理学观察发现2-甲基呋喃的暴露能够造成明显的肝肾组织纤维化，空泡样变，细胞间隙增大等，进一步证实了2-甲基呋喃造成的肝肾损伤。肝脏中Nrf2和HO-1的含量升高，而且具有剂量依赖性。本项目的实施，将为食品热加工过程中2-甲基呋喃的安全控制技术奠定理论基础，为2-甲基呋喃在热加工食品中暴露的安全性评价及其限量标准的制定提供科学依据。课题研究成果发表5篇SCI收录论文，其中2篇被JCR一区收录，其余3篇为JCR二区，培养硕士研究生4名，完成了规定的任务指标。...