食品危害物丙烯酰胺诱导神经毒性中MPO/H2O2/HClO分子氧化体系的作用及机制

食品加工过程中会生成许多类危害物，研究食品危害物对人体的毒性作用及机制可为毒性干预及限量标准的制定提供科学依据。丙烯酰胺（ACR）是淀粉食品在高温下产生的典型化学危害物，主要导致人体神经毒性伤害，但关于作用机制的报道十分有限。近期研究表明ACR致神经毒性中脑内活性氧水平明显增高同时髓过氧化物酶（MPO）的活性显著增加，基于氧化应激和脑神经细胞损伤的研究基础，我们推测MPO/H2O2/HClO分子氧化体系形成的HClO氧化应激在ACR神经毒性机制中发挥作用。本项目拟通过体内外实验，采用MPO/H2O2/HClO分子体系拮抗剂和MPO siRNA干扰分子表达的手段，分析MPO/H2O2/HClO体系在ACR致大鼠神经毒性机制中的作用，探讨MPO/H2O2/HClO体系分子表达对ACR诱导胶质细胞及神经元损伤的影响。研究结果力争为ACR神经毒性机制及毒性干预研究提供新线索。

Many Kinds of hazards are introduced during food processing. Studies on toxicity and mechanism of these hazards might provide scientific evidences for toxicity intervention and the establishment of limit standard. Acrylamide (ACR), a typical chemical hazard produced in the high-temperature starch-based food processing, shows severe neurotoxicity in human body. However, the mechanism is still unclear. Recent studies have found that the activity of myeloperoxidase (MPO) significantly increased in the neurotoxicity induced by ACR, which suggested the expression of MPO might be involved in ACR neurotoxicity mechanism. Based on previous researches on oxidative stress and cranial nerve system injury we predicted that the oxidative stress induced by MPO/H2O2/HClO system might play a role in the ACR neurotoxicity mechanism, on which has still no related reports focused. This project plans to use inhibitor of MPO/H2O2/ HClO, MPO siRNA cells to determine the role of MPO/H2O2/HClO expression in rat neurotoxicity induced by ACR in vivo and in vitro. This study also explores the effect of MPO/H2O2/HClO on the damage of neuron and glial cells induced by ACR. Furthermore, this study attempts to serve new clues for ACR neurotoxicity mechanism and toxicity intervention.