摘要
镉(Cd)是一种重要的环境污染物,可造成蓄积机体包括肝脏在内多种器官的损害。本研究旨在揭示Cd暴露对小鼠肝脏组织铁死亡的作用及其机制。24只8周龄ICR小鼠随机平均分为对照组和3个Cd暴露组(Cd组),Cd组每日给小鼠腹腔注射1、2、3 mg/kg的氯化镉(CdCl2),对照组注射等体积的生理盐水,连续7 d。8 d后处死小鼠,分别观察肝脏组织病理学及超微结构变化,检测血清中肝功能酶(ALT、AST)活性,肝脏组织中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)和Cd的含量,检测铁死亡相关因子的蛋白表达水平。结果显示,Cd暴露后肝脏组织间质充血,肝脏细胞索消失、线粒体出现絮状致密物,嵴缺失空化。Cd暴露组小鼠血清ALT和AST,肝脏组织MDA和Cd含量显著升高,肝脏组织GSH-Px含量显著下降(P<0.01)。肝脏组织ACSL4、HO-1蛋白表达量极显著升高(P<0.01),GPX4、SLC7A11、FTH1、FTL蛋白的表达量则极显著下降(P<0.01)。结果表明,Cd暴露可致ICR小鼠肝脏组织铁代谢紊乱,抗氧化水平降低,脂质过氧化,从而介导肝脏发生铁死亡。本研究为进一步完善Cd暴露致肝损伤的毒性机制提供了重要的理论依据。
Cadmium(Cd)is an important environmental toxicant that can cause serious damage to various organs including severe hepatotoxicity in intoxicated animals.The purpose of this study is to reveal the role and mechanism of Cd exposure on ferroptosis in mice liver.Twenty-four 8-weekold ICR mice were randomly divided into the control group and 3 cadmium exposure groups(group Cd).Mice in the Cd group were injected with CdCl_2 of 1,2 and 3 mg/kg intraperitoneally every day,while the control group was injected with the same volume of saline for 7 days.All mice were killed on the 8th day,and the histopathological and ultra-pathological changes of liver were observed.The activity of liver functional enzymes(ALT,AST)in serum,the contents of malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and Cd in liver and the protein expression levels of ferroptosis related factors were detected,The results showed that interstitial congestion of liver,loss of hepatocyte cords,flocculent dense substance in mitochondria and matrix degeneration ridge were observed in liver of the CdCl_2 treatment mice.The results showed that serum levels of ALT and AST,the contents of MDA and Cd in liver were increased significantly,while the activity of GSH-Px in liver was significantly decreased(P<0.01)in CdCl_2 exposed mice.Protein levels of GPX4,SLC7A11,FTH1 and FTL were decreased significantly,but protein levels of ACSL4 and HO-1 were significantly increased in CdCl_2 exposed mice.Thereby,Cd exposure caused disruption of iron metabolism in mice liver,decreased antioxidant levels and lipid peroxidation in ICR mice,mediating the occurrence of liver ferroptosis.This study provides an important theoretical data for further improving the hepatotoxicity mechanism of Cd exposure.
作者
郁孝强
吴亚
罗通旺
宋圣哲
王书杰
宋厚辉
邵春艳
YU Xiaoqiang;WU Ya;LUO Tongwang;SONG Shengzhe;WANG Shujie;SONG Houhui;SHAO Chunyan(Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province/Zhejiang Provincial Engineering Laboratory for Animal Health Inspection&Internet Technology/Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management/China-Australia Joint Laboratory for Animal Health Big Data Analytics,College of Animal Science and Technology&College of Veterinary Medicine of Zhejiang A&F University,Hangzhou 311300,China)
出处
《中国兽医学报》
CAS
CSCD
北大核心
2024年第3期543-549,共7页
Chinese Journal of Veterinary Science
基金
浙江农林大学科研发展基金人才启动基金资助项目(2020FR045)
浙江省大学生科技创新活动计划暨新苗人才计划资助项目(2023R412021)。
关键词
镉
小鼠
肝脏
铁死亡
cadmium
mice
liver
ferroptosis
作者简介
共同第一作者:郁孝强(1997-),男,硕士研究生;共同第一作者:吴亚(2001-),女,本科;通信作者:宋厚辉,Email:songhh@zafu.edu.cn;通信作者:邵春艳,Email:shaocy@zafu.edu.cn。
