微塑料联合MEHP抑制SIRT3/SOD2诱导肝细胞线粒体损伤和氧化应激  

Microplastics Combined with MEHP Induced Mitochondrial Damage and Oxidative Stress via Inhibiting SIRT3/SOD2 in Hepatocytes

作　　者：王晓曼 石东星 韩艳阳 董亚静 韩浩[1,2,3,4] Wang Xiaoman;Shi Dongxing;Han Yanyang;Dong Yajing;Han Hao(School of Public Health,Shanxi Medical University,Taiyuan 030001,China;Nutritional and Food Sciences Research Institute,Shanxi Medical University,Taiyuan 030001,China;MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China;Center for Ecological Public Health Security of Yellow River Basin,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学公共卫生学院,太原030001 [2]山西医科大学营养与食品科学研究所,太原030001 [3]山西医科大学煤炭环境致病与防治教育部重点实验室,太原030001 [4]山西医科大学黄河流域生态公共卫生安全研究中心,太原030001

出　　处：《生态毒理学报》2024年第3期363-372,共10页Asian Journal of Ecotoxicology

基　　金：山西省应用基础研究计划基金项目(202103021223223);山西省应用基础研究计划基金项目(202303021211124)。

摘　　要：微塑料(microplastics,MPs)常与多种塑料相关产品共同暴露损害人体健康。邻苯二甲酸二(2-乙基己基)酯(di-2-ethylhexyl phthalate,DEHP)是常见的塑化剂,其主要代谢物为邻苯二甲酸单(2-乙基己基)酯(mono-2-ethylhexyl phthalate,MEHP)。MPs与MEHP进入机体后均在肝脏蓄积,因此研究MPs与MEHP的联合暴露对肝脏的毒性效应及潜在机制具有重要意义。本研究采用聚苯乙烯微塑料(polystyrene microplastics,PS-MPs)和MEHP单独及二者联合处理HepG2细胞,检测细胞活力、活性氧水平、线粒体膜电位、COXⅠ、COXⅢ、SIRT3和SOD2的蛋白表达水平。结果表明,PS-MPs和MEHP单独暴露均引起活性氧生成增加、线粒体膜电位降低。PS-MPs单独暴露也导致COXⅠ与COXⅢ蛋白表达水平降低。两者联合暴露时上述有害作用更为显著,为协同效应。进一步的分子机制研究表明,PS-MPs下调了SIRT3和SOD2蛋白表达,MEHP下调了SIRT3蛋白表达,而PS-MPs和MEHP联合暴露对SIRT3和SOD2的蛋白表达的影响表现为协同效应。综上所述,PS-MPs和MEHP联合暴露导致HepG2细胞氧化应激和线粒体损伤,其分子机制与抑制SIRT3/SOD2信号通路有关。Microplastics(MPs)are usually co-exposed with a variety of plastic-related products.This co-exposed is harmful to human health.Mono-2-ethylhexyl phthalate(MEHP)is a primary metabolite of di-2-ethylhexyl phthalate(DEHP),a common plasticizer.Once entering into the body,MPs and MEHP accumulate in the liver.Therefore,it is important to study the toxic effects of the co-exposed of MPs and MEHP on the liver and explore the potential mechanisms.In this study,HepG2 cells were treated with polystyrene microplastics(PS-MPs),MEHP,or PS-MPs combined with MEHP.The cell viability,reactive oxygen species(ROS),mitochondrial membrane p otential(MMP),and protein expression of COXⅠ,COXⅢ,SIRT3 and SOD2 were measured.The results showed that PS-MPs or MEHP exposure increased ROS generation and decreased MMP.PS-MPs exposure alone reduced protein expression of COXⅠand COXⅢ.These harmful effects were more pronounced when combined exposure,indicated a synergistic effect.Further molecular mechanism study exhibited that PS-MPs treatment down-regulated the protein expression of SIRT3 and SOD2.MEHP treatment down-regulated the protein expression of SIRT3.The combined exposure of PS-MPs and MEHP synergistically down-regulated the protein expression of SIRT3 and SOD2.In summary,the combined exposure of PS-MPs and MEHP resulted in oxidative stress and m itochondrial damage in HepG2 cells,and the underlying molecular mechanism is related to the inhibition of the SIRT3/SOD2 signaling pathway.

关 键 词：微塑料 MEHP HEPG2细胞 联合暴露 氧化应激 线粒体损伤 SIRT3 

分 类 号：X171.5[环境科学与工程—环境科学]