壬基酚诱导肝细胞氧化损伤及铁死亡机制研究  

Study on mechanism of nonylphenol induced oxidative damage and iron death in hepatocytes

作　　者：王雨欣 陈丹娜 雷卓凡 邹颜璐 曹唱唱 宋泉江 宋厚辉[1,2,3,4,5] 姜胜 WANG Yuxin;CHEN Danna;LEI Zhuofan;ZOU Yanlu;CAO Changchang;SONG Quanjiang;SONG Houhui;JIANG Sheng(College of Veterinary Medicine of Zhejiang A&F University,Hangzhou,311300,China;Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province,Hangzhou,311300,China;Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics&Advanced Technology,Hangzhou,311300,China;Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management,Hangzhou,311300,China;China-Australia Joint Laboratory for Animal Health Big Data Analytics,Hangzhou,311300,China)

机构地区：[1]浙江农林大学动物医学学院,浙江杭州311300 [2]浙江省畜禽绿色生态健康养殖应用技术研究重点实验室,浙江杭州311300 [3]动物健康互联网检测技术浙江省工程研究中心,浙江杭州311300 [4]浙江省动物医学与健康管理国际科技合作基地,浙江杭州311300 [5]中澳动物健康大数据分析联合实验室,浙江杭州311300

出　　处：《中国兽医学报》2024年第8期1793-1799,共7页Chinese Journal of Veterinary Science

基　　金：浙江省新苗人才计划资助项目(2022R412A025)。

摘　　要：旨在研究壬基酚(nonylphenol,NP)致肝细胞损伤的机制。通过建立NP诱导BRL-3A肝细胞损伤体外模型,评估肝细胞氧化损伤标志物变化、肝细胞Fe^(2+)含量变化,观察肝细胞超微结构,检测铁死亡标志蛋白表达水平。结果显示,NP可引起BRL-3A细胞ROS、MDA显著升高(P<0.05);GSH含量、GSH-Px活性和SOD活性显著降低(P<0.05);Fe^(2+)含量显著升高(P<0.05),并呈现剂量依赖性;BRL-3A细胞线粒体体积明显变小,线粒体嵴断裂甚至消失,有的线粒体呈现空泡化;铁稳态相关蛋白TFR1和FTH1蛋白表达水平显著降低(P<0.05)。结果表明,铁死亡参与NP诱导肝细胞损伤机制,为深入探究NP致病机理提供了参考。The aim of this experiment is to investigate the mechanism of liver cell damage induced by nonylphenol(NP).After establishing an in vitro model of NP induced BRL-3A liver cell injury,changes of oxidative damage markers were evaluated,Fe^(2+)content was determined,the ultrastructure of BRL-3A was observed,and the expression level of iron death marker proteins were determined.The results showed that NP could significantly increase ROS and MDA in BRL-3A cells(P<0.05);the GSH content,GSH Px activity,and SOD activity were significantly reduced(P<0.05);the Fe^(2+)content significantly increased(P<0.05)and showed a dose-dependent effect;the mitochondrial volume of BRL-3A cells significantly decreases,the mitochondrial cristae break or even disappear,and some mitochondria show vacuolization;the expression levels of iron homeostasis related proteins TFR1 and FTH1 were significantly reduced(P<0.05).The results indicate that ferroptosis is involved in the mechanism of NP induced liver cell damage,which benefits for further exploration of NP pathogenesis.

关 键 词：铁死亡 氧化损伤 壬基酚 BRL-3A细胞 

分 类 号：S853.7[农业科学—临床兽医学]