摘要
目的:探讨铁死亡是否参与大鼠肺缺血-再灌注损伤(LIRI),以及缺血预处理(I-pre-C)是否通过抑制铁死亡而减轻LIRI。方法:将SPF级雄性SD大鼠随机分成4组:对照组(control组),缺血-再灌注(IR)30 min组(IR组)、铁死亡抑制剂去铁胺(DFO)组(IR+DFO组)和I-pre-C组,进行指标检测及肺脏病理观察。使用光镜、电镜和二氢乙啶(DHE)染色等评估大鼠肺组织的损伤程度;Western blot等方法检测缺血-再灌注肺组织铁死亡的相关指标。结果:与control组相比,IR组肺组织的活性氧(ROS)水平升高,丙二醛(MDA)和Fe水平升高,谷胱甘肽(GSH)水平下降,铁死亡相关蛋白酰基辅酶A合成酶长链家族成员4(ACSL4)和转铁蛋白受体1(TFR1)水平升高,铁蛋白重链1(FTH1)、谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11)下降(P<0.01);与IR组相比,IR+DFO组肺组织的ROS水平显著下降,铁死亡的线粒体形态有所改善,MDA水平下降,GSH水平上升(P<0.01);与IR组相比,I-pre-C明显改善了大鼠肺组织损伤,肺组织ROS水平显著下降(P<0.01),且能够降低IR引起的MDA水平和Fe的累积,升高GSH水平,同时有效调控铁死亡相关蛋白的水平,包括下调ACSL4和TFR1及上调FTH1和GPX4水平(P<0.01)。结论:铁死亡参与大鼠LIRI;抑制铁死亡能够有效缓解IR引起的肺损伤;I-pre-C通过抑制铁死亡而减轻大鼠LIRI。
AIM:To investigate whether ferroptosis is involved in lung ischemia-reperfusion injury(LIRI) in rats and whether ischemic preconditioning(I-pre-C) attenuates LIRI by inhibiting ferroptosis. METHODS:The SPF male SD rats were randomly divided into 4 groups:control group, ischemia-reperfusion(IR) group, ferroptosis inhibitor deferoxamine(DFO) group(DFO+IR group), and I-pre-C group. Indexes were detected and lung pathology was observed. The degree of lung injury was evaluated by light microscopy, electron microscopy and dihydroethidium(DHE) staining. The degree of ferroptosis involved in LIRI was evaluated by survival test. The indicators related to ferroptosis in lungs were detected by Western blot. RESULTS:Compared with control group, the levels of reactive oxygen species(ROS) were increased, the levels of MDA and Fe in the lungs were increased, and the levels of GSH were decreased in IR group(P<0. 01). The levels of ferroptosis-related proteins ACSL4 and TFR1 were increased, and FTH1 and GPX4 were decreased(P<0. 01). Compared with IR group, the ROS level in the lung tissue of DFO+IR group was significantly decreased, the ferroptosis morphology of mitochondria was improved, the MDA level was decreased, and the GSH level was increased(P<0. 01). Compared with IR group, I-pre-C improved lung tissue structure, significantly decreased lung ROS level(P<0. 01), reduced IR-induced MDA level and Fe accumulation, increased GSH level, and effectively improved the levels of ferroptosis-related proteins, including inhibiting ACSL4 and TFR1, and increasing FTH1 and GPX4(P<0. 01). CONCLUSION:Ferroptosis is involved in LIRI in rats. Inhibition of ferroptosis can effectively attenuate lung injury caused by IR. Ischemic preconditioning attenuates LIRI by inhibiting ferroptosis in rats.
作者
盛小飞
王淑远
王新雨
王肖婷
田云娜
宋正阳
徐俊鹏
刘秀洁
王万铁
SHENG Xiaofei;WANG Shuyuan;WANG Xinyu;WANG Xiaoting;TIAN Yun-na;SONG Zhengyang;XU Junpeng;LIU Xiujie;WANG Wantie(Department of Gastroenterology,The First People's Hospital of Lin'an District,Lin'an 311300,China;Department of Respiratory Medicine,Third People's Hospital,Wenzhou 325000,China;Institute of Ischemia Reperfusion Injury,Wen-zhou Medical University,Wenzhou 325035,China.)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2023年第1期117-122,共6页
Chinese Journal of Pathophysiology
基金
浙江省卫生健康科技计划项目(No.2022KY1070)
浙江省介入肺脏病重点实验室建设项目(No.2019E10014)。
关键词
铁死亡
肺缺血-再灌注损伤
大鼠
缺血预处理
氧化应激
ferroptosis
lung ischemia-reperfusion injury
rats
ischemic preconditioning
oxidative stress
