铁死亡在急性镉诱导小鼠肝损伤中的作用  

Role of ferroptosis in acute cadmium-induced liver injury in mice

作　　者：殷杞子 唐玉婷 张赛君 郭思宇 李婧 王子悦 姬艳丽 YIN Qizi;TANG Yuting;ZHANG Saijun;GUO Siyu;LI Jing;WANG Ziyue;JI Yanli(Department of Health Inspection and Quarantine,School of Public Health,Anhui Medical University,Hefei 230032,China;The First Clinical School of Medicine,Anhui Medical University,Hefei 230032,China)

机构地区：[1]安徽医科大学公共卫生学院卫生检验与检疫学系,合肥230032 [2]安徽医科大学第一临床医学院,合肥230032

出　　处：《广西医科大学学报》2024年第12期1588-1594,共7页Journal of Guangxi Medical University

基　　金：国家自然科学基金面上项目(No.31571557);安徽省质量工程项目(No.2023cxtd036);安徽医科大学2024年度大学生创新创业项目(No.X202410366070)。

摘　　要：目的:探讨铁死亡在急性镉诱导小鼠肝损伤中的作用。方法:健康清洁级8~10周的ICR雄鼠,随机分为对照组(con‐trol组)和镉暴露组。镉暴露组经腹腔注射给予等量4 mg·kg^(-1) CdCl_(2),分别于CdCl_(2)处理6 h、12 h和24 h后取肝脏组织及血液。对照组同样处理方式给予等容量生理盐水。采用苏木精—伊红(HE)染色法观察小鼠肝脏组织的病理损伤。采用试剂盒检测小鼠血清中ALT、AST、总铁、GSH、SOD、H_(2)O_(2)和MDA的含量。采用实时荧光定量PCR(RT-qPCR)和蛋白质免疫印迹(west‐ern blotting)法检测小鼠肝脏组织铁死亡关键基因的表达。结果:急性镉暴露降低小鼠肝脏重量及其脏器系数,明显引起肝脏功能及病理损伤。与对照组相比,镉暴露组GSH和SOD的含量降低,ALT、AST和MDA含量增加,H_(2)O_(2)的含量显著增加(P<0.05)。此外,镉显著增加小鼠肝脏总铁含量,诱导小鼠肝脏组织HO-1和FTH1的蛋白表达,而GPX4蛋白表达在镉暴露组显著降低(P<0.05)。结论:急性镉暴露导致肝脏氧化应激,增加肝脏中的铁含量,改变肝脏中与铁死亡相关的基因的转录和蛋白质的表达,提示铁死亡可能参与急性镉暴露诱导的肝损伤。Objective:To investigate the role of ferroptosis in acute liver injury induced by cadmium(Cd)expo‐sure in mice.Methods:Healthy and clean male ICR mice of 8-10 weeks were randomly divided into control group,and Cd exposure group.The mice in the Cd exposure group were injected with an equal amount of CdCl_(2)(4 mg·kg^(-1))intraperitoneally.Liver tissues and blood were collected after Cd treatment for 6h,12h and 24h,re‐spectively.The mice in the control group were injected with normal saline in the same way.The hematoxylin-eosin(HE)staining method was used to observe the pathological injury of liver.The contents of ALT,AST,total iron,GSH,SOD,H_(2)O_(2) and MDA in serum were detected by corresponding kits.The expression of key genes of ferroptosis in liver tissues of mice were detected by real-time fluorescence quantitative PCR(RT-qPCR)and west‐ern blotting.Results:The acute Cd exposure reduced liver weight and organ coefficient in mice,and significantly caused liver function and pathological damage.Compared with the control group,the contents of GSH and SOD in the Cd exposure group were decreased,the contents of ALT,AST,and MDA were increased,and the content of H_(2)O_(2) was significantly increased(P<0.05).In addition,Cd significantly increased the total iron content in liver of mice,induced the protein expression of HO-1 and FTH1 in liver tissue of mice,while the protein expression of GPX4 was significantly decreased in the Cd exposure group(P<0.05).Conclusion:Acute Cd exposure can cause oxidative stress,increase iron content,and alter transcription and protein expression of genes associated with ferroptosis in the liver,suggesting that ferroptosis may be involved in liver injury induced by acute Cd expo‐sure.

关 键 词：铁死亡 镉 肝脏 氧化应激 

分 类 号：R575[医药卫生—消化系统]