铁死亡在自体原位肝移植大鼠肺损伤中的作用  

Role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation

作　　者：吴威[1,2] 包旭 韦金珍 王永旺 王刚 谭永星 卜文豪 Wu Wei;Bao Xu;Wei Jinzhen;Wang Yongwang;Wang Gang;Tan Yongxing;Bu Wenhao(Department of Anesthesiology,CR&WISCO General Hospital,Affiliated to Wuhan University of Science and Technology,Wuhan 430080,China;Department of Anesthesiology,Graduate School of Guilin Medical University,Guilin 541001,China;Department of Anesthesiology,Affiliated Hospital of Guilin Medical University,Guilin 541000,China;Department of Anesthesiology,Guilin Munipical Hospital of Traditional Chinese Medicine,Guilin 541000,China;Department of Anesthesiology,Maternal and Child Health Hospital of Hubei Province,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430064,China)

机构地区：[1]武汉科技大学附属华润武钢总医院麻醉科,武汉430080 [2]桂林医学院研究生学院麻醉学系,桂林541001 [3]桂林医学院附属医院麻醉科,桂林541000 [4]桂林市中医医院麻醉科,桂林541000 [5]华中科技大学同济医学院附属湖北省妇幼保健院麻醉科,武汉430064

出　　处：《中华麻醉学杂志》2023年第3期359-362,共4页Chinese Journal of Anesthesiology

基　　金：广西区自然科学基金项目(2022JJA140025,2022JJA140020);桂林市科学研究与开发计划项目(2020011204-15,20210227-4)。

摘　　要：目的评价铁死亡在自体原位肝移植大鼠肺损伤中的作用。方法健康成年SPF级雄性SD大鼠24只,8~10周龄,体质量230~270 g,采用随机数字表法分为3组(n=8):假手术组(S组)、自体原位肝移植组(LT组)和自体原位肝移植+铁死亡抑制剂Ferrostain-1组(LT+Fer-1组)。LT组和LT+Fer-1组建立原位自体肝移植模型,LT+Fer-1组于术前30 min腹腔注射Ferrostain-15 mg/kg。于再灌注6 h时取下腔静脉血标本,麻醉后处死大鼠取肺组织。观察肺组织病理学结果,并行肺损伤评分;采用ELISA法测定血清MDA浓度、肺组织MDA、还原性谷胱甘肽(GSH)、谷胱甘肽过氧化物酶4(GPX4)和Fe^(2+)含量;采用Western blot法测定铁蛋白重链1(FTH1)和溶质载体家族7成员11重组蛋白(SLC7A11)的表达。结果与S组比较,LT组肺损伤评分、血清MDA浓度、肺组织MDA和Fe^(2+)含量升高,GSH和GPX4含量降低,FTH1和SLC7A11表达下调(P<0.05);与LT组比较,LT+Fer-1组肺损伤评分、血清MDA浓度、肺组织MDA和Fe^(2+)含量降低,GSH和GPX4含量升高,FTH1和SLC7A11表达上调(P<0.05)。结论铁死亡参与了自体原位肝移植大鼠肺损伤的病理生理过程。Objective To evaluate the role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation.Methods Twenty-four healthy adult SPF-grade male rats,aged 8-10 weeks,weighing 230-270 g,were divided into 3 groups(n=8 each)using the random number table method:sham operation group(S group),autologous in situ liver transplantation group(LT group)and ferroptosis inhibitor Ferrostain-1 group(LT+Fer-1 group).In LT group and LT+Fer-1 group,an autologous in situ liver transplantation model was developed in anesthetized animals,and Ferrostain-15 mg/kg was intraperitoneally injected at 30 min before surgery in LT+Fer-1 group.The inferior vena cava blood samples were obtained at 6 h of reperfusion,then animals were sacrificed,and lung tissues were obtained.The morphology of lung tissues was examined,and the lung injury was scored.The serum malondialdehyde(MDA)concentration and contents of MDA,reduced glutathione(GSH),glutathione peroxidase4(GPX4),and Fe^(2+)in lung tissues were measured by enzyme-linked immunosorbent assay.The expression of ferritin heavy chain 1(FTH1)and solute carrier family 7 member 11 recombinant protein(SLC7A11)was determined by Western blot.Results Compared with S group,the lung injury,serum MDA concentration,and contents of MDA and Fe^(2+)were significantly increased,the contents of GSH and GPX4 were decreased,and the expression of FTH1 and SLC7A11 was down-regulated in LT group(P<0.05).Compared with LT group,the lung injury,serum MDA concentration,and contents of MDA and Fe^(2+)were significantly decreased,the contents of GSH and GPX4 were increased,and the expression of FTH1 and SLC7A11 was up-regulated in LT+Fer-1 group(P<0.05).Conclusions Ferroptosis is involved in the pathophysiology of lung injury in a rat model of autologous orthotopic liver transplantation.

关 键 词：肝移植 急性肺损伤 铁死亡 

分 类 号：R657.3[医药卫生—外科学]