邻苯二甲酸酯类污染物(PAEs)暴露对外周血携氧和免疫功能的影响与机制研究

As a kind of widespread and important organic pollutants, PAEs can affect blood function in vivo. The toxic effects and mechanisms of PAEs on blood are important scientific issues urgently needed to be resolved to protect human health. In this project, we plan to combine the in vivo and in vitro experiments, molecular docking and molecular dynamics simulations to clarify the scientific issues at the levels of cell, cellular membrane and molecule by: studying the structure-activity relationships for the damage of common PAEs and their metabolites to the main physiological functions of peripheral blood (oxygen carrying and immune); exploring the injury mechanisms of PAEs on the oxygen carrying capacity of peripheral blood (iron release of hemoglobin) from the aspects of the binding of PAEs with the hemoglobin in the red blood cells, and the oxidative stress induced by PAEs; analyzing the toxic mechanisms of PAEs and its metabolites on the immune function of peripheral blood (changes of the contents or functions of the immune cells and molecules) from the perspectives of cell membrane fluidity and oxidative stress. Through the study, we expect to expound the toxic effects and mechanisms of PAEs to the oxygen carrying and immune functions of peripheral blood in vivo from the point of hematological toxicology, and provide scientific methods and reference basis for health risk assessment of PAEs in the environment and formulating intervention measures.

邻苯二甲酸酯类污染物(PAEs)是环境中广泛存在的、重要的有机污染物，进入机体后对血液功能产生影响，其对血液的毒性效应及作用机理是保护人体健康急需阐明的重要科学问题。本项目拟将体内、外实验，分子对接和分子动力学模拟相结合，在细胞、细胞膜、分子水平上研究常见PAEs及其代谢产物对外周血主要生理功能(携氧和免疫)产生损伤的构效关系；从PAEs与红细胞内血红蛋白结合、诱导红细胞氧化应激等方面探讨PAEs对外周血携氧能力损伤(血红蛋白铁释放)的机制；从细胞膜流动性和氧化应激两个角度分析PAEs及其代谢产物对外周血免疫功能毒性(免疫细胞和免疫分子含量或功能改变)的机理来解决上述科学问题。通过本研究，有望从血液毒理学视角揭示PAEs在机体内对外周血携氧和免疫功能的毒性效应与机制，为环境中PAEs的健康危险度评价及制定预防措施提供科学方法和参考依据。

邻苯二甲酸酯类污染物(PAEs)是环境中广泛存在的、重要的有机污染物，进入机体后对血液功能产生影响，其对血液的毒性效应及作用机理是保护人体健康急需阐明的重要科学问题。本项目结合体内和体外实验从血液毒理学角度研究了典型PAEs邻苯二甲酸二甲酯(DMP)对外周血主要生理功能(携氧和免疫)的影响及机制。结果表明，DMP会降低红细胞的抗氧化能力，诱导其氧化应激，导致血红蛋白铁释放，从而影响血液的携氧功能。DMP能引起红细胞脂质过氧化损伤，改变细胞膜微环境，影响C3b受体，从而破坏红细胞的免疫功能。DMP能够通过引起机体发生氧化应激和诱导细胞凋亡相关基因表达导致血液免疫细胞发生凋亡，从而造成免疫细胞数目减少，进而使免疫活性物质含量下降，最终损害血液免疫功能。本研究可为环境中PAEs的健康危险度评价及制定预防措施提供科学方法和参考依据。