铁死亡参与阿霉素诱导的小鼠局灶节段性肾小球硬化  

Ferroptosis is involved in the adriamycin-induced focal segmental glomurular sclerosis in mice

作　　者：于晓霞 王洪梅[1] 朱虹 吴华[1] 郑明楠[1] 朴明姬[1] 边艳 高弼虎[1] Yu Xiaoxia;Wang Hongmei;Zhu Hong;Wu Hua;Zheng Mingnan;Piao Mingji;Bian Yan;Gao Bihu(Department of Nephrology,Affiliated Zhongshan Hospital of Dalian University,Dalian 116001,China)

机构地区：[1]大连大学附属中山医院肾内科,辽宁116001

出　　处：《国际医药卫生导报》2021年第15期2260-2263,共4页International Medicine and Health Guidance News

基　　金：辽宁省自然科学基金项目(2019-ZD-0307);大连市中医药医学科学研究计划项目(20Z11001)。

摘　　要：目的观察铁死亡在阿霉素(ADR)诱导小鼠局灶节段性肾小球硬化(FSGS)中的作用。方法雄性BALB/c小鼠按完全随机设计分为对照组和模型组,每组20只。模型组采用眼球后静脉注射ADR建立小鼠FSGS,对照组于眼球后注射与ADR同等剂量的生理盐水。实验第0周、第1周和第8周分别检测两组小鼠尿白蛋白/肌酐(ACR)。实验第8周末,处死小鼠,取肾组织,分别在多聚甲醛和戊二醛中固定,病理切片经PAS染色和透射电镜观察;试剂盒检测肾组织中谷胱甘肽(GSH)和丙二醛(MDA)水平;荧光定量聚合酶链式反应(qRT-PCR)检测肾组织中前列腺素内过氧化物合酶2(PTGS2)mRNA表达。结果第8周末,模型组小鼠ACR为(78.57±21.64)mg/mg,对照组小鼠ACR为(17.96±5.86)mg/mg,模型组显著高于对照组(P<0.001);肾组织PAS染色呈典型局灶、节段性肾小球硬化表现,提示造模成功。超微结构显示,模型组小鼠足细胞中线粒体萎缩,线粒体膜密度增加和膜破裂。与对照组比较,模型组小鼠肾组织GSH浓度显著减少[(6.49±2.63)mmol/L比(3.92±1.86)mmol/L],MDA浓度显著增高[(35.69±5.28)mmol/L比(73.36±12.47)mmol/L],PTGS2 mRNA表达水平显著升高[(1.34±1.61)比(5.94±3.51)],均P<0.001。结论ADR诱导小鼠FSGS过程中存在铁死亡现象,提示铁死亡可能参与FSGS的发生。Objective To observe the role of ferroptosis in adriamycin-induced focal segmental glomurular sclerosis(FSGS)in mice.Methods The male BALB/c mice were randomly divided into a control group and a model group,with 20 cases in each group.The mouse models of FSGS nephropathy in the model group were established by the retroeyeball injection of adriamycin.The control group took the retroeyeball injection of normal saline of the same volume.At week 0,1,and 8,the microalbuminuria/creatatine(ACR)was detected in both groups.At week 8,the mice were kill for kidney tissue,and the tissue was fixed in paraformaldehyde and glutaraldehyde.The pathological slices were dyed by PAS and observed by a transmission electron microscope.The glutathione(GSH)and malondialdehyde(MDA)levels in the kidney tissue were measured by corresponding assay kits.The expression level of prostaglandin-endoperoxide synthase 2(PTGS2)mRNA was detected by quantitative polymerase chain reaction(qPCR).Results At week 8,the ACR was(78.57±21.64)in the model group,and was(17.96±5.86)in the control group(P<0.001).After being dyed by PAS,the kidney tissue showed typical focal segmental glomurular sclerosis,indicating that the models were done.The ultramicrostructure showed that the mitochondrias of podocytes were shrunken,the mitochondrial membranes'density increased,and the mitochondrial membranes ruptured in the model group.The GSH concentration was lower and the MDA concentration and the PTGS 2 mRNA level were higher in model group than in the control group[(6.49±2.63)mmol/L vs.(3.92±1.86)mmol/L,(35.69±5.28)mmol/L vs.(73.36±12.47)mmol/L,and(1.34±1.61)vs.(5.94±3.51);all P<0.001].Conclusion Ferroptosis occurrs during adriamycin-induced FSGS in mice,suggesting that ferroptosis plays a potential role in the pathogenesis of FSGS in mouse models.

关 键 词：铁死亡 阿霉素 局灶节段性肾小球硬化 

分 类 号：R692.6[医药卫生—泌尿科学]