全氟烷基物质在猪鸡的比较代谢研究

Perfluoronic compounds (PFCs) are a new class of persistent organic compound and widely present in animal body all over the world. PFCs were found to have multiple biological toxicity. Moreover, it has been demonstrated that the toxicity of PFCs has species difference, which was closely associated with metabolism of PFCs. However, the mechanism of their metabolism was still poorly understood. The research about the effects of PFCs on the mechanism of metabolism of swine and chicken will be carried out. The metabolites of PFCs will be identified. Furthermore, the relationship of metabolism and animal species, metabolism and compound structure will be interpreted. The target enzymes in the metabolism of the PFCs will be found by analysis the subtypes of CYP450 enzymes in swine and chicken. During the research, more technologies, such as liquid chromatography-ion trap/time-of-flight mass spectrometry (LC/MS-IT-TOF), liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS), real-time reverse transcriptional polymerase chain reaction (real-time PCR), and Western blot were used to reveal the species differences of metabolic enzymes in the levels of genes and proteins. It was much worth paying more continuing attention to the PFCs-induced mechanism of metabolism for its benefit to provide a theoretical basis study on toxicity of PFCs. Furthermore, it was also benefit to identify residual marker and biological marker of PFCs in animal and improve the food safety of animal.

全氟烷基物质（PFCs）是一种新型的持久有机污染物，在动物体内广泛存在，具有多种生物毒性，且存在动物种属毒性差异特性。这种毒性差异与动物体内代谢相关，而其在动物体内代谢差异机制一直未得到深入研究。本课题综合利用液相色谱-离子阱-飞行时间联用仪、液相色谱-三级四级杆质谱仪、实时荧光定量PCR、Western blot等多种技术和手段，鉴定猪和鸡体内PFCs代谢物，阐明代谢与动物种属关系，代谢与化合物结构关系，同时对猪和鸡P450 酶系进行亚型分析，挖掘参与PFCs代谢相关靶酶，比较猪鸡不同食品动物间P450对代谢PFCs活性差异，从代谢角度、基因和蛋白质水平揭示PFCs在食品动物代谢差异机制。深入研究PFCs代谢机制，对PFCs毒性机制研究提供理论支撑，对确定PFCs在动物体内的残留标志物和生物标志物具有重要作用，对保障动物食品安全具有重要意义。

全氟烷基物质是一类新型持久有机污染物，具有多种生物毒性作用。这些化合物的毒性呈现结构和动物种属差异特性，这与全氟烷基物质在不同动物体内代谢效应密切相关。本项目依照计划任务书，通过建立猪鸡肝微粒体和肝细胞体外代谢系统，采用LC-MS-IT-TOF质谱定性方法和LC-MS/MS质谱定量方法鉴定全氟烷基物质类化合物在猪鸡体外代谢系统和体内的代谢物；建立猪和鸡组织样品中全氟烷基物质及其代谢物的定量方法，开展全氟烷基物质类化合物在猪和鸡体内的残留消除规律研究；采用肝微粒体体外代谢，通过特异性酶抑制技术对参与全氟烷基物质类化合物代谢的P450酶进行研究，确定关键代谢酶，并进行克隆表达。通过上述系列的研究，阐明了全氟烷基物质类化合物在猪鸡的代谢特点、规律和种属差异。有助于了解全氟烷基物质潜在的生物学毒性，对于全面评估全氟烷基物质在食品动物体内的生物蓄积性及其它有害作用具有十分重要的意义。