铁死亡在大鼠心肌缺血-再灌注损伤中的作用  

The role of ferroptosis in myocardial ischemia-reperfusion injury in rats

作　　者：赵述傲 朱仪章 濮雨凌 李子千 杜逸之 陈可 张潇月 杨红宁 顾文华 丁梦媛 刘江锡 杨婉婷 周翔 燕宪亮 Zhao Shu-ao;Zhu Yi-zhang;Pu Yu-ling;Li Zi-qian;Du Yi-zhi;Chen Ke;Zhang Xiao-yue;Yang Hong-ning;Gu Wen-hua;Ding Meng-yuan;Liu Jiang-xi;Yang Wan-ting;Zhou Xiang;Yan Xian-liang(Department of Emergency and Rescue Medicine,Xuzhou Medical University,Xuzhou 221004,China)

机构地区：[1]徐州医科大学急救与救援医学系,江苏徐州221004 [2]徐州医科大学附属医院急诊医学科,江苏徐州221004 [3]江苏省第二中医院急诊科,江苏南京210017

出　　处：《中国急救医学》2022年第1期53-57,共5页Chinese Journal of Critical Care Medicine

基　　金：江苏省高等学校大学生创新创业训练计划项目(201810313006Z);基础医学国家级实验教学示范中心(徐州医科大学)资助项目;江苏省教育厅“青蓝工程”优秀教学团队(53041801);徐州市国家临床重点专科培育资助项目(2018ZK004);江苏省卫生健康委“六个一”工程科研资助项目(LGY2019085);徐州医科大学附属医院优秀中青年人才资助项目(2019128009)。

摘　　要：目的用大鼠心肌细胞氧糖剥夺(oxygen glucose deprivation,OGD)/复灌(rexyenation,R)模型模拟大鼠心肌缺血-再灌注损伤(myocardial ischemia-reperfusion injury,MIRI),研究铁死亡(Ferroptosis)及其在大鼠MIRI中的作用。方法采用体外培养的大鼠H9c2心肌细胞,分为正常培养组(Control组)、铁死亡激动剂组(Erastin组)、氧糖剥夺/复灌组(OGD/R组)、溶剂对照组(OGD/R+DMSO组)和Ferroptosis抑制剂组(OGD/R+Fer-1组)。分别采用光学显微镜观察各实验组的细胞数目,CCK-8法检测不同实验组细胞活力,透射电子显微镜(TEM)观察不同实验组H9c2细胞超微结构的变化。结果光学显微镜观察到使用Ferroptosis抑制剂(Fer-1,0.5μmol/L)后,细胞死亡减少;CCK-8结果显示,Ferroptosis特异性抑制剂Fer-1可部分减轻复灌后引起的细胞生长抑制(P<0.001);电镜结果显示,OGD/R后H9c2细胞出现Ferroptosis特异性超微形态改变:脂质沉积增多,线粒体明显皱缩及双层脂质膜密度增加。结论大鼠H9c2心肌细胞OGD/R后存在Ferroptosis,Ferroptosis能够降低细胞活力导致细胞死亡。Objective To investigate whether the ferroptosis exists in the oxygen glucose deprivation/reperfusion(OGD/R)of rat cardiomyocyte models,and its role in rat myocardial ischemia-reperfusion injury.Methods The H9 c2 rat myocardial cells cultured in vitro were divided into the normal group(control group),Erastin group,OGD/R group,vehicle control group(OGD/R+DMSO group),inhibitor group(OGD/R+Fer-1 group).Transmission electron microscope(TEM)was used to observe the changes of ultra microstructure of H9 c2 cells in different experimental groups;Cell viability was detected with CCK-8;The cell morphology of each group was observed by optical microscopy.Results The optical microscopy observed that ferroptosis specific inhibitor(Fer-1,0.5μmol/L)protected the cells.CCK-8 results showed that Fer-1 could partially alleviate the OGD/R injury induced cell growth inhibition(P<0.001).TEM results indicated that morphological change of ferroptosis specific ultra microstructure were observed in H9 c2 cells after OGD/R injury,such as the increase of lipid deposition,mitochondrial shrinkage and the increase of bilayer lipid membrane density.Conclusions The presence of ferroptosis in H9 c2 myocytes after OGD/R in rats.Ferroptosis induced cell death by reducing cell viability.

关 键 词：心肌细胞 铁死亡(Ferroptosis) 氧糖剥夺/复灌(OGD/R) 铁死亡特异性抑制剂(Ferrostatin-1 Fer-1) 心肌缺血-再灌注损伤(MIRI) 

分 类 号：R542.22[医药卫生—心血管疾病]