双酚F引起的脂质降解能力降低引发非酒精性脂肪性肝病脂质积聚的作用研究  

In vitro study on the role of reduced lipid degradation capacity induced by bisphenol F in triggering lipid accumulation in nonalcoholic fatty liver disease

作　　者：张林伟 薛璟 肖杭[1] 高蓉[3] 王军 ZHANG Linwei;XUE Jing;XIAO Hang;GAO Rong;WANG Jun(Department of Toxicology,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Taizhou Center for Disease Control and Prevention,Taizhou,Jiangsu 225300,China;Department of Laboratory Medicine,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China)

机构地区：[1]南京医科大学公共卫生学院卫生毒理学系,江苏南京211166 [2]泰州市疾病预防控制中心,江苏泰州225300 [3]南京医科大学公共卫生学院卫生检验系,江苏南京211166

出　　处：《职业卫生与应急救援》2023年第2期215-219,253,共6页Occupational Health and Emergency Rescue

基　　金：江苏省自然科学基金面上项目(BK20211252);江苏省高校自然科学研究重大项目(21KJA330002)。

摘　　要：目的从脂质降解角度,阐述双酚F(bisphenol F,BPF)暴露对肝脏细胞HepG2脂质降解能力、脂肪酸氧化、活性氧(reactive oxygen species,ROS)水平三方面的影响。方法采用HepG2构建体外染毒模型,通过实时聚合酶链式反应(polymerase chain reaction,PCR)、共聚焦显微镜检测及Western blot等实验技术,观察BPF对HepG2细胞的脂质降解途径的影响。结果BPF暴露引起HepG2细胞脂质水解限速酶———脂肪三酰甘油脂肪酶及激素敏感性脂肪酶mRNA及蛋白表达减少(P<0.05);脂肪酸氧化相关蛋白———肉碱棕榈酰转移酶1α(CPT1α)、过氧化物酶体增殖物激活受体α(PPARα)mRNA及蛋白表达降低(P<0.05),线粒体来源的ROS水平升高(P<0.01);最终导致脂滴积聚。结论BPF暴露致HepG2细胞脂质降解和脂肪酸氧化能力降低,以及线粒体来源ROS水平升高,可能是造成非酒精性脂肪性肝病样改变发生的重要原因之一。Objective From the perspective of lipid degradation,the effects of bisphenol F(BPF)exposure on lipolysis,fatty acid oxidation,and reactive oxygen species(ROS)levels in HepG2 cells were described.Methods HepG2 cells were used to construct an in vitro exposure model.The effects of BPF on the lipid degradation pathway were observed by realtime quantitative PCR,confocal microscopy,and Western blot.Results BPF exposure reduced the mRNA and protein expression of the rate-limiting enzymes,adipose triglyceride lipase(ATGL)and hormone-sensitive lipase(HSL),in HepG2 cells(P<0.05).The mRNA and protein expressions of the fatty acid oxidation-related proteins,carnitine palmitoyl transferase 1α(CPT1α)and peroxisome proliferator-activated receptorα(PPARα),were decreased(P<0.05),and the ROS level from mitochondria was increased(P<0.01).This caused the accumulation of lipid droplets.Conclusions BPF exposure reduced lipolysis and fatty acid oxidation in HepG2 cells and increased the level of ROS derived from mitochondria,which may be one of the important reasons for the occurrence of nonalcoholic fatty liver disease(NAFLD)-like changes.

关 键 词：双酚F 非酒精性脂肪性肝病 脂质降解 脂肪酸氧化 活性氧 

分 类 号：R114[医药卫生—卫生毒理学]