切换至 "中华医学电子期刊资源库"

中华移植杂志(电子版) ›› 2025, Vol. 19 ›› Issue (01) : 43 -49. doi: 10.3877/cma.j.issn.1674-3903.2025.01.008

移植巾帼论坛

肾移植缺血再灌注损伤机制及其对移植肾的影响
李一萱1, 李美和1, 郑瑾1,()   
  1. 1. 710061 西安,西安交通大学第一附属医院肾病医院肾移植科 西安交通大学器官移植研究所
  • 收稿日期:2024-08-30 出版日期:2025-02-25
  • 通信作者: 郑瑾
  • 基金资助:
    国家自然科学基金项目(82170768)

Mechanism of ischemia-reperfusion injury in renal transplantation and its impact on transplanted kidneys

Yixuan Li1, Meihe Li1, Jin Zheng1,()   

  1. 1. Department of Kidney Transplantation, Organ Transplant Institute, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
  • Received:2024-08-30 Published:2025-02-25
  • Corresponding author: Jin Zheng
引用本文:

李一萱, 李美和, 郑瑾. 肾移植缺血再灌注损伤机制及其对移植肾的影响[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 43-49.

Yixuan Li, Meihe Li, Jin Zheng. Mechanism of ischemia-reperfusion injury in renal transplantation and its impact on transplanted kidneys[J/OL]. Chinese Journal of Transplantation(Electronic Edition), 2025, 19(01): 43-49.

肾移植手术不可避免地要经历肾脏缺血和血液再灌注的过程,造成移植肾缺血再灌注损伤(IRI),其与术后早期移植物功能恢复和长期存活密切相关,且目前临床上仍缺乏明确有效的防治手段。深入研究移植肾IRI的发生机制能够为研发新型保护策略提供理论基础和科学依据,本文就肾移植IRI机制及其对移植肾的影响进行综述。

The process of kidney transplantation surgery inevitably involves a phase of kidney ischemia and reperfusion, resulting in damage to the kidney's ischemia-reperfusion injury (IRI),which is intimately linked to the initial functional recuperation and prolonged survival of the transplanted organ. Presently, definitive and efficacious methods for clinical prevention and treatment remain elusive. A thorough examination of how IRI functions in transplanted kidneys offers both theoretical and scientific foundations for creating novel protective approaches. This review discusses the mechanisms of IRI and its impact on renal allograft.

图1 肾移植缺血再灌注损伤的生理机制 注: ATP.三磷酸腺苷; ROS.活性氧
图2 细胞死亡机制图 注: 应用MedPeer绘制; Fe(II).二价铁离子; Fe(III).三价铁离子; DMT1.二价金属转运蛋白1; ZIP.锌转运蛋白; LIP.活性铁池;PCBP1/2.铁离子分子伴侣; LOX.脂氧合酶; RSL3.谷胱甘肽过氧化物酶抑制剂; GSH.还原型谷胱甘肽; GSSG.氧化型谷胱甘肽; GPX4.谷胱甘肽过氧化物酶4; PARP.多聚ADP核糖聚合酶; Fas.CD95; FADD.Fas相关死亡域蛋白; casp.半胱氨酸天冬氨酸蛋白水解酶; RIPK.丝氨酸/苏氨酸蛋白激酶; MLKL.混合谱系激酶结构域样蛋白; TNF.肿瘤坏死因子; APAF1.衔接蛋白酶活化因子1; XIAP.X连锁凋亡抑制蛋白;Bcl-2.B细胞淋巴瘤因子2; BAD.Bcl-2相关死亡启动子; Drp1.动力蛋白相关蛋白1; BAX.Bcl-2相关X蛋白; LPS.脂多糖; GSDMD.Gasdermin-D,一种由细胞质感知侵袭性感染和危险信号而引发的炎症性细胞死亡的介质; DAMPs.损伤相关分子模式; mTOR.哺乳动物雷帕霉素靶蛋白; Atg.自噬相关基因; FIP.粘着斑激酶家族相互作用蛋白; ULK.Unc-51样激酶; AMBRA.自噬和Beclin调节器; PI3K.III型磷脂酰肌醇激酶
图3 移植肾纤维化发生机制 注: 应用MedPeer绘制; Wnt.无翅型MMTV病毒整合位点家族; DVL.蓬乱蛋白; Snail 1.Snail同源物1重组蛋白; Twist.TWIST转录因子重组蛋白; PAI-1.纤溶酶原激活物抑制物-1; MMP7.基质金属蛋白酶7; Fn1.纤维连接蛋白1; Cd44.膜整合蛋白; Nos2.诱导型一氧化氮合酶
1
Zhao H, Alam A, Soo AP, et al. Ischemia-reperfusion injury reduces long term renal graft survival: mechanism and beyond[J].EBioMedicine, 2018, 28: 31-42.
2
Ornellas FM, Ornellas DS, Martini SV, et al. Bone marrow-derived mononuclear cell therapy accelerates renal ischemia-reperfusion injury recovery by modulating inflammatory, antioxidant and apoptotic related molecules[J]. Cell Physiol Biochem, 2017, 41(5): 1736-1752.
3
Tejchman K, Kotfis K, Sieńko J. Biomarkers and mechanisms of oxidative stress-last 20 years of research with an emphasis on kidney damage and renal transplantation[J]. Int J Mol Sci, 2021, 22(15):8010.
4
Su L, Zhang J, Gomez H, et al. Mitochondria ROS and mitophagy in acute kidney injury[J]. Autophagy, 2023, 19(2): 401-414.
5
Raedschelders K, Ansley DM, Chen DD. The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion[J]. Pharmacol Ther, 2012, 133(2): 230-255.
6
Li J, Cao F, Yin HL, et al. Ferroptosis: past, present and future[J]. Cell Death Dis, 2020, 11(2): 88.
7
Wu J, Wang Y, Jiang R, et al. Ferroptosis in liver disease: new insights into disease mechanisms[J]. Cell Death Discov, 2021, 7(1): 276.
8
Dar WA, Sullivan E, Bynon JS, et al. Ischaemia reperfusion injury in liver transplantation: cellular and molecular mechanisms[J]. Liver Int, 2019, 39(5): 788-801.
9
Dugbartey GJ. Cellular and molecular mechanisms of cell damage and cell death in ischemia-reperfusion injury in organ transplantation[J].Mol Biol Rep, 2024, 51(1): 473.
10
Luo Y, Zhou S, Xu T, et al. SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury[J]. Chin Med J(Engl), 2023, 136(20): 2496-2507.
11
Bigham NP, Wilson JJ. Metal coordination complexes as therapeutic agents for ischemia-reperfusion injury[J]. J Am Chem Soc, 2023,145(17): 9389-9409.
12
Newton K, Strasser A, Kayagaki N, et al. Cell death[J]. Cell,2024, 187(2): 235-256.
13
Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death[J]. Cell Mol Immunol,2021, 18(5): 1106-1121.
14
Thomas K, Zondler L, Ludwig N, et al. Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells[J]. JCI Insight, 2022, 7(21):e163161.
15
Li F, Mao Q, Wang J, et al. Salidroside inhibited cerebral ischemia/reperfusion-induced oxidative stress and apoptosis via Nrf2/Trx1 signaling pathway[J]. Metab Brain Dis, 2022,37(8):2965-2978.
16
D'Arcy MS. Cell death: a review of the major forms of apoptosis,necrosis and autophagy[J]. Cell Biol Int, 2019, 43(6): 582-592.
17
Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death[J]. Nat Rev Mol Cell Biol, 2020,21(2):85-100.
18
Qi Y, Hu M, Wang Z, et al. Mitochondrial iron regulation as an emerging target in ischemia/reperfusion injury during kidney transplantation[J]. Biochem Pharmacol, 2023, 215: 115725.
19
Kaltenmeier C, Wang R, Popp B, et al. Role of immunoinflammatory signals in liver ischemia-reperfusion injury[J]. Cells,2022, 11(14):2222.
20
Saeed WK, Jun DW, Jang K, et al. Does necroptosis have a crucial role in hepatic ischemia-reperfusion injury?[J]. PLoS One, 2017,12(9): e0184752.
21
Chen X, Zhu R, Zhong J, et al. Mosaic composition of RIP1-RIP3 signalling hub and its role in regulating cell death[J]. Nat Cell Biol,2022, 24(4): 471-482.
22
Tong X, Tang R, Xiao M, et al. Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis,ferroptosis, and cuproptosis research[J]. J Hematol Oncol, 2022,15(1): 174.
23
Decuypere JP, Ceulemans LJ, Agostinis P, et al. Autophagy and the kidney: implications for ischemia-reperfusion injury and therapy[J]. Am J Kidney Dis, 2015, 66(4): 699-709.
24
Li CJ, Liao WT, Wu MY, et al. New insights into the role of autophagy in tumor immune microenvironment[J]. Int J Mol Sci,2017, 18(7):1566.
25
Kesavardhana S, Malireddi RKS, Kanneganti TD. Caspases in cell death, inflammation, and pyroptosis[J]. Annu Rev Immunol, 2020,38: 567-595.
26
Zhao H, Yang Y, Si X, et al. The role of pyroptosis and autophagy in ischemia reperfusion injury[J]. Biomolecules, 2022, 12(7):1010.
27
Smith SF, Hosgood SA, Nicholson ML. Ischemia-reperfusion injury in renal transplantation: 3 key signaling pathways in tubular epithelial cells[J]. Kidney Int, 2019, 95(1): 50-56.
28
Lasorsa F, Rutigliano M, Milella M, et al. Ischemia-reperfusion injury in kidney transplantation:mechanisms and potential therapeutic targets[J]. Int J Mol Sci, 2024, 25(8):4332.
29
Santarsiero D, Aiello S. The complement system in kidney transplantation[J]. Cells, 2023, 12(5):791.
30
Tang SP, Mao XL, Chen YH, et al. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death[J]. Front Immunol, 2022, 13: 870239.
31
Granata S, La Russa D, Stallone G, et al. Inflammasome pathway in kidney transplantation[J]. Front Med (Lausanne), 2023, 10:1303110.
32
Lv S, Liu H, Wang H. The interplay between autophagy and NLRP3 inflammasome in ischemia/reperfusion injury[J]. Int J Mol Sci,2021, 22(16):8773.
33
Huang G, Bao J, Shao X, et al. Inhibiting pannexin-1 alleviates sepsis-induced acute kidney injury via decreasing NLRP3 inflammasome activation and cell apoptosis[J]. Life Sci, 2020, 254: 117791.
34
Jia Y, Cui R, Wang C, et al. Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway[J]. Redox Biol, 2020, 32: 101534.
35
Su X, Liu B, Wang S, et al. NLRP3 inflammasome: a potential therapeutic target to minimize renal ischemia/reperfusion injury during transplantation[J]. Transpl Immunol, 2022, 75: 101718.
36
Jadlowiec CC, Frasco P, Macdonough E, et al. Association of DGF and early readmissions on outcomes following kidney transplantation[J]. Transpl Int, 2022, 35: 10849.
37
Puttarajappa CM, Jorgensen D, Yabes JG, et al. Trends and impact on cold ischemia time and clinical outcomes using virtual crossmatch for deceased donor kidney transplantation in the United States[J].Kidney Int, 2021, 100(3): 660-671.
38
Andras I, Piana A, Verri P, et al. Systematic review of techniques and devices used to avoid warm ischemia time injury during kidney transplantation[J]. World J Urol, 2023, 41(4): 993-1003.
39
Barba J, Zudaire JJ, Robles JE, et al. Is there a safe cold ischemia time interval for the renal graft?[J]. Actas Urol Esp, 2011,35(8):475-480.
40
Benichou G, Yamada Y, Yun SH, et al. Immune recognition and rejection of allogeneic skin grafts[J]. Immunotherapy, 2011, 3(6):757-770.
41
Zhou H, Lu H, Sun L, et al. Diagnostic biomarkers and immune infiltration in patients with T cell-mediated rejection after kidney transplantation[J]. Front Immunol, 2021, 12: 774321.
42
Liu Y, Pu X, Qin X, et al. Neutrophil extracellular traps regulate HMGB1 translocation and kupffer cell M1 polarization during acute liver transplantation rejection[J]. Front Immunol, 2022, 13: 823511.
43
Brenner BM, Lawler EV, Mackenzie HS. The hyperfiltration theory:a paradigm shift in nephrology[J]. Kidney Int, 1996,49(6):1774-1777.
44
Helal I, Fick-Brosnahan GM, Reed-Gitomer B, et al. Glomerular hyperfiltration: definitions, mechanisms and clinical implications[J].Nat Rev Nephrol, 2012, 8(5): 293-300.
45
Chen J, Layton AT, Edwards A. A mathematical model of O2 transport in the rat outer medulla. I. Model formulation and baseline results[J]. Am J Physiol Renal Physiol, 2009, 297(2): F517-F536.
46
Molitoris BA, Sutton TA. Endothelial injury and dysfunction: role in the extension phase of acute renal failure[J]. Kidney Int, 2004, 66(2): 496-499.
47
Legrand M, Mik EG, Johannes T, et al. Renal hypoxia and dysoxia after reperfusion of the ischemic kidney[J]. Mol Med, 2008, 14(7-8): 502-516.
48
魏军军, 楼仲冠, 楼江涌, 等. 慢性移植肾间质纤维化的发病机制及其治疗的研究进展[J]. 中华器官移植杂志, 2017, 38(11):699-703.
49
Nickerson PW. Rationale for the IMAGINE study for chronic active antibody-mediated rejection (caAMR) in kidney transplantation[J].Am J Transplant, 2022, 22 Suppl 4: 38-44.
50
Norman JT, Clark IM, Garcia PL. Hypoxia promotes fibrogenesis in human renal fibroblasts[J]. Kidney Int, 2000, 58(6): 2351-2366.
51
Zhang M, Liu Q, Meng H, et al. Ischemia-reperfusion injury:molecular mechanisms and therapeutic targets[J]. Signal Transduct Target Ther, 2024, 9(1): 12.
52
Dufour L, Ferhat M, Robin A, et al. Ischemia-reperfusion injury after kidney transplantation[J]. Nephrol Ther, 2020, 16(6): 388-399.
53
Zheng J, Lan P, Li M, et al. Anti-Na+/K+-ATPase DR antibody attenuates UUO-induced renal fibrosis through inhibition of Na+/K+-ATPase α1-dependent HMGB1 release[J]. Int Immunopharmacol,2023, 116: 109826.
54
Yan X, Xun M, Dou X, et al. Activation of Na+-K+-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na+-K+-ATPase/Src/Ros amplifier[J]. Apoptosis, 2017,22(4): 531-543.
[1] 王馨悦, 王卓然, 古丽莎. 氧化纳米铈促进氧化应激状态下口腔骨缺损修复的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2025, 19(01): 62-69.
[2] 孙瑜博, 陈瑞, 翟亦晖, 汤梁峰, 张致庆, 王春燕, 耿红全, 沈茜, 刘锋, 徐虹. 合并膀胱功能障碍儿童肾移植受者疗效评估[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 2-8.
[3] 陈晓彬, 聂晓晶, 翁增凤, 刘婧婧, 黄隽. PAX2基因变异致Papillorenal综合征儿童肾移植四例[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 9-15.
[4] 姜梦婕, 黄淑娟, 裴瑜馨, 容丽萍, 许园园, 林知朗, 丘原全, 刘龙山, 蒋小云, 陈丽植. 儿童复发性移植肾肾病临床特点及诊治[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 16-21.
[5] 曾锦华, 韩新利, 徐虹, 翟亦晖, 刘锋, 陈瑞, 方晓燕, 张致庆, 王春燕, 陈径, 沈茜. 儿童肾移植受者移植后淋巴组织增生性疾病临床特点及诊治[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 22-25.
[6] 金小艳, 邓芳, 方韶晗, 丁亚婷. 儿童肾移植受者心脏结构及功能分析[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 26-30.
[7] 余成军, 张杰, 裴军, 孔繁森, 杨舒媛, 吴盛德, 刘星, 温晟, 华燚, 魏光辉. 终末期肾病儿童肾移植临床特征和疗效分析[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 31-35.
[8] 李道文, 张鹏, 陈正, 方佳丽. 实体器官移植对脑结构和功能影响的研究进展[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 50-53.
[9] 王明君, 李宁, 李燕, 尚丽红, 郭文萍, 吕广娜, 武媛婷, 武小桐. 补体结合的供者特异性抗体对稳定期肾移植受者预后影响的临床总结[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 54-59.
[10] 王国辉, 韩士超, 戚若晨, 张小燕, 徐桐, 张阳, 范效铮, 魏迪, 刘克普, 马帅军, 杨晓剑, 秦卫军. 异种移植——猪供肾获取手术方案经验交流[J/OL]. 中华移植杂志(电子版), 2025, 19(01): 60-64.
[11] 王奇, 李林峰, 林启盛, 龚朝阳, 连文清, 龙永富, 黄亚强. 广东省医学会泌尿外科疑难病例多学科会诊(第23期)——VHL综合征并双侧肾细胞癌[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(02): 272-277.
[12] 唐敏英, 邬绿莹, 陈津, 路君, 吴仲秋. 肾移植术后BKV 肾病免疫细胞浸润及关键基因分析[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(01): 12-19.
[13] 吕园园, 高辰旸, 徐永君. 纳米金棒对A549 细胞的毒性效应及其对自噬的影响[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(01): 20-29.
[14] 李杨春雪, 高杰, 郭文治, 刘智. 远端缺血预处理器官保护与年龄相关性差异研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(12): 1150-1154.
[15] 杨毅, 申珅, 万孟夏, 张拥波. 术前外周血炎症指标对颈动脉支架置入术后同侧新发无症状缺血性脑损伤的预测价值[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(01): 13-18.
阅读次数
全文


摘要