代谢重编程在脓毒症相关急性肾损伤中的研究进展

doi:10.3969/j.issn.1004-583X.2025.08.015

摘要/Abstract

摘要：

脓毒症相关急性肾损伤(sepsis-associated acute kidney injury,SA-AKI)是重症监护病房常见的危重并发症,具有高发病率和高死亡率。代谢重编程(最初在癌症研究中被称为Warburg效应)是SA-AKI的关键病理机制。脓毒症发生时,炎症细胞与肾实质细胞的代谢模式向有氧糖酵解转换,可放大促炎反应并增强细胞对脓毒症打击的抵抗能力。随着病程进展,这些细胞代谢模式则恢复为氧化磷酸化,进而促进抗炎反应并增强功能修复。代谢重编程和线粒体动力学紊乱是SA-AKI能量代谢异常的核心环节。本文系统综述了代谢重编程在SA-AKI发病机制及治疗干预中的最新研究进展,旨在为开发针对性的SA-AKI治疗策略提供理论依据。

关键词: 脓毒症, 急性肾损伤, 代谢重编程, 发病机制, 治疗

中图分类号:

R692
R459.7

武媛媛, 孟舰. 代谢重编程在脓毒症相关急性肾损伤中的研究进展[J]. 临床荟萃, 2025, 40(8): 753-757.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2025.08.015

https://www.lchc.cn/CN/Y2025/V40/I8/753

参考文献 47

[1]	Zarbock A, Nadim MK, Pickkers P, et al. Sepsis-associated acute kidney injury: Consensus report of the 28th Acute Disease Quality Initiative workgroup[J]. Nat Rev Nephrol, 2023, 19(6):401-417. doi: 10.1038/s41581-023-00683-3 pmid: 36823168
[2]	Takeuchi T, Flannery AH, Liu LJ, et al. Epidemiology of sepsis-associated acute kidney injury in the ICU with contemporary consensus definitions[J]. Crit Care, 2025, 29(1):128.
[3]	Pais T, Jorge S, Lopes JA. Acute kidney injury in sepsis[J]. Int J Mol Sci, 2024, 25(11):5924.
[4]	Wang T, Huang Y, Zhang X, et al. Advances in metabolic reprogramming of renal tubular epithelial cells in sepsis-associated acute kidney injury[J]. Front Physiol, 2024,15:1329644.
[5]	Dyck B, Unterberg M, Adamzik M, et al. The impact of pathogens on sepsis prevalence and outcome[J]. Pathogens, 2024, 13(1):89.
[6]	Nath S, Balling R. The Warburg effect reinterpreted 100 yr on: A first-principles stoichiometric analysis and interpretation from the perspective of ATP metabolism in cancer cells[J]. Function (Oxf), 2024, 5(3):zqae008.
[7]	Wu H, Huang H, Zhao Y. Interplay between metabolic reprogramming and post-translational modifications: From glycolysis to lactylation[J]. Front Immunol, 2023,14:1211221.
[8]	Turgut F, Awad AS, Abdel-Rahman EM. Acute kidney injury: Medical causes and pathogenesis[J]. J Clin Med, 2023, 12(1):375.
[9]	Liu J, Cheng Y, Zhang X, et al. Glycosyltransferase Extl1 promotes CCR7-mediated dendritic cell migration to restrain infection and autoimmunity[J]. Cell Rep, 2023, 42(1):111991.
[10]	Sukonina V, Ma H, Zhang W, et al. FOXK1 and FOXK2 regulate aerobic glycolysis[J]. Nature, 2019, 566(7743): 279-283.
[11]	Zhou L, Li H, Hu J, et al. Plasma oxidative lipidomics reveals signatures for sepsis-associated acute kidney injury[J]. Clin Chim Acta, 2023, 551: 117616.
[12]	Gong N, Wang W, Fu Y, et al. The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease[J]. Cell Mol Biol Lett, 2025, 30(1): 72.
[13]	Liu TF, Vachharajani VT, Yoza BK, et al. NAD+-dependent sirtuin 1 and 6 proteins coordinate a switch from glucose to fatty acid oxidation during the acute inflammatory response[J]. J Biol Chem, 2012, 287(31):25758-25769. doi: 10.1074/jbc.M112.362343 pmid: 22700961
[14]	Zhong L, D'Urso A, Toiber D, et al. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1α[J]. Cell, 2010, 140(2): 280-293. doi: 10.1016/j.cell.2009.12.041 pmid: 20141841
[15]	Chu W, Sun X, Yan Y. Study on the regulation of renal tubular cell apoptosis by SIRT1/NF-κB signaling pathway in septic acute kidney injury[J]. Ren Fail, 2025, 47(1): 2499904.
[16]	Tan C, Gu J, Li T, et al. Inhibition of aerobic glycolysis alleviates sepsis? induced acute kidney injury by promoting lactate/Sirtuin 3/AMPK-regulated autophagy[J]. Int J Mol Med, 2021, 47(3):19.
[17]	Gómez H. Reprogramming metabolism to enhance kidney tolerance during sepsis: The role of fatty acid oxidation, aerobic glycolysis, and epithelial de-differentiation[J]. Nephron, 2023, 147(1):31-34.
[18]	Lee LE, Doke T, Mukhi D, et al. The key role of altered tubule cell lipid metabolism in kidney disease development[J]. Kidney Int, 2024, 106(1):24-34. doi: 10.1016/j.kint.2024.02.025 pmid: 38614389
[19]	Kocemba-Pilarczyk KA, Ostrowska B, Trojan SE, et al. Deciphering enemy tactics-the narrow path to an optimal anti-cancer strategy targeting the Warburg effect[J]. Pharmacol Rep, Published online August 1, 2025.
[20]	Pomeyie K, Abrokwah F, Boison D, et al. Macrophage immunometabolism dysregulation and inflammatory disorders[J]. Biomed Pharmacother, 2025,188:118142.
[21]	Xu S, Deng KQ, Lu C, et al. Interleukin-6 classic and trans-signaling utilize glucose metabolism reprogramming to achieve anti-or pro-inflammatory effects[J]. Metabolism, 2024,155:155832.
[22]	Sica A, Mantovani A. Macrophage plasticity and polarization: In vivo veritas[J]. J Clin Invest, 2012, 122(3):787-795. doi: 10.1172/JCI59643 pmid: 22378047
[23]	Lv Y, Li Z, Liu S, et al. Metabolic checkpoints in immune cell reprogramming: Rewiring immunometabolism for cancer therapy[J]. Mol Cancer, 2025, 24(1):210.
[24]	张霖柯, 赵志伶, 李廷翠, 等. 巨噬细胞在脓毒性心肌病发病机制中的作用[J]. 中华危重病急救医学, 2025, 37(3): 305-309.
[25]	Ma H, Gao L, Chang R, et al. Crosstalk between macrophages and immunometabolism and their potential roles in tissue repair and regeneration[J]. Heliyon, 2024, 10(18):e38018.
[26]	Van den Bossche J, Baardman J, de Winther MP. Metabolic characterization of polarized M1 and M2 bone marrow-derived macrophages using real-time extracellular flux analysis[J]. J Vis Exp, 2015,(105):53424.
[27]	Cao Q, Huang C, Yi H, et al. A single-domain i-body, AD-114, attenuates renal fibrosis through blockade of CXCR4[J]. JCI Insight, 2022, 7(4):e143018.
[28]	Ni Y, Wu GH, Cai JJ, et al. Tubule-mitophagic secretion of SerpinG1 reprograms macrophages to instruct anti-septic acute kidney injury efficacy of high-dose ascorbate mediated by NRF2 transactivation[J]. Int J Biol Sci, 2022, 18(13):5168-5184. doi: 10.7150/ijbs.74430 pmid: 35982894
[29]	Sun Z, Lv R, Zhao Y, et al. Communications between neutrophil-endothelial interaction in immune defense against bacterial infection[J]. Biology (Basel), 2024, 13(6):374.
[30]	Aklilu A, Lai MS, Jiang Z, et al. Immunothrombosis in sepsis: Cellular crosstalk, molecular triggers, and therapeutic opportunities-A review[J]. Int J Mol Sci, 2025, 26(13):6114.
[31]	Shaoqun T, Xi Y, Wei W, et al. Neutrophil extracellular traps-related genes contribute to sepsis-associated acute kidney injury[J]. BMC Nephrol, 2025, 26(1):235.
[32]	Chen S, Zhang Q, Sun L, et al. HP promotes neutrophil inflammatory activation by regulating PFKFB2 in the glycolytic metabolism of sepsis[J]. PLoS One, 2024, 19(1):e0296266.
[33]	Huang P, Liu Y, Li Y, et al. Correction: Metabolomics-and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury[J]. BMC Med, 2025, 23(1):143.
[34]	Smith JA, Stallons LJ, Schnellmann RG. Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury[J]. Am J Physiol Renal Physiol, 2014, 307(4):F435-F444.
[35]	Jaiswal A, Singh R. A negative feedback loop underlies the Warburg effect[J]. NPJ Syst Biol Appl, 2024, 10(1):55. doi: 10.1038/s41540-024-00377-x pmid: 38789545
[36]	徐丽, 孙鹏. 脓毒症相关性急性肾损伤的识别和管理[J]. 中华危重病急救医学, 2023, 35(2): 221-224.
[37]	Fang T, Ma C, Zhang Z, et al. Roxadustat, a HIF-PHD inhibitor with exploitable potential on diabetes-related complications[J]. Front Pharmacol, 2023,14:1088288.
[38]	Harris E. FDA approves first oral treatment for kidney disease-induced anemia[J]. JAMA, 2023, 329(9):704.
[39]	Qiao J, Tan Y, Liu H, et al. Histone H3K18 and ezrin lactylation promote renal dysfunction in sepsis-associated acute kidney injury[J]. Adv Sci (Weinh), 2024, 11(28):e2307216.
[40]	Ishihara SI, Kayes MI, Makino H, et al. The PKM2 activator TEPP-46 suppresses cellular senescence in hydrogen peroxide-induced proximal tubular cells and kidney fibrosis in CD-1db/db mice[J]. J Diabetes Investig, 2025, 16(4):598-607.
[41]	Luo P, Zhang Q, Zhong TY, et al. Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect[J]. Mil Med Res, 2022, 9(1):22. doi: 10.1186/s40779-022-00381-4 pmid: 35596191
[42]	Iajun W, Kaifeng G, Jing Z. Urinary PKM2, a marker predicating acute kidney injury in patients with sepsis[J]. Int Urol Nephrol, 2024, 56(9):3039-3045. doi: 10.1007/s11255-024-04054-0 pmid: 38635124
[43]	Xie W, He Q, Zhang Y, et al. Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury[J]. Cell Death Dis, 2023, 14(10):663. doi: 10.1038/s41419-023-06195-z pmid: 37816709
[44]	Sun C, Xiong H, Guo T. β-nicotinamide mononucleotide alleviates sepsis-associated acute kidney injury by activating NAD+/SIRT3 signaling[J]. Cell Biochem Biophys, 2025, 83(2):2089-2099.
[45]	Dai Q, Zhang H, Tang S, et al. Vitamin D-VDR (vitamin D receptor) alleviates glucose metabolism reprogramming in lipopolysaccharide-induced acute kidney injury[J]. Front Physiol, 2023,14:1083643.
[46]	Xu C, Hong Q, Zhuang K, et al. Regulation of pericyte metabolic reprogramming restricts the AKI to CKD transition[J]. Metabolism, 2023,145:155592.
[47]	Sun M, Wang F, Li H, et al. Maresin-1 attenuates sepsis-associated acute kidney injury via suppressing inflammation, endoplasmic reticulum stress and pyroptosis by activating the AMPK/SIRT3 pathway[J]. J Inflamm Res, 2024,17:1349-1364.

代谢重编程在脓毒症相关急性肾损伤中的研究进展

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 47

相关文章 15

编辑推荐

Metrics

本文评价

[1]	庄蕙萃, 郭皓, 李贤, 崔东升. 血流感染合并脓毒症患者预后危险因素及其预测价值分析[J]. 临床荟萃, 2025, 40(8): 698-704.
[2]	马良, Severine Martin, 孙广东. 基于加蓬数据的疟疾相关急性肾损伤患者临床特征分析[J]. 临床荟萃, 2025, 40(8): 717-720.
[3]	赵伟, 徐慧娟, 赵艳霞, 王玲珍, 卢愿, 杨静. 婴儿恶性石骨症1例并文献复习[J]. 临床荟萃, 2025, 40(8): 726-730.
[4]	陈文江, 舒展, 周来显. 基于核酸适配体的肺癌诊断和治疗研究进展[J]. 临床荟萃, 2025, 40(8): 742-747.
[5]	孙楠, 杨凯琦, 唐亚赛, 谢小华, 吕佩源, 董艳红. 帕金森病认知障碍的治疗新进展[J]. 临床荟萃, 2025, 40(8): 748-752.
[6]	卢远思, 吕见君, 官计彬, 操龙斌. 双相情感障碍患者外周血中FGF1的表达与糖脂代谢的相关性[J]. 临床荟萃, 2025, 40(7): 619-623.
[7]	孙振晓, 于相芬. 皮肤搔抓障碍的研究进展[J]. 临床荟萃, 2025, 40(7): 647-652.
[8]	毛静静, 兰云霞, 陈鲁玉, 宋先荣. A型主动脉夹层合并肠系膜上动脉缺血的研究进展[J]. 临床荟萃, 2025, 40(7): 659-662.
[9]	何媛, 王俭. 特发性脊柱侧凸患者神经与结构影像相关改变的研究进展[J]. 临床荟萃, 2025, 40(7): 669-672.
[10]	林彬城, 林刚曦. 病因、术前病程对药物难治性癫痫患儿疗效的影响[J]. 临床荟萃, 2025, 40(6): 527-531.
[11]	王思晗, 李向红, 李亮亮, 锡洪敏, 杨萍, 马丽丽, 尹向云. 新生儿RYR1相关肌病1例并文献复习[J]. 临床荟萃, 2025, 40(6): 541-546.
[12]	孙振晓, 于相芬. 幻肢痛的临床治疗进展[J]. 临床荟萃, 2025, 40(6): 570-576.
[13]	刘萍, 于猛, 刘明新, 李文锋. 血常规衍生的新型炎症指标与急性前壁ST段抬高型心肌梗死患者PCI术后院内发生不良心血管事件的相关性[J]. 临床荟萃, 2025, 40(5): 400-407.
[14]	赵雅静, 陶千山, 沈元元, 董毅. 地西他滨维持治疗对适合强化疗中低危急性髓细胞白血病患者生存的影响[J]. 临床荟萃, 2025, 40(5): 439-444.
[15]	范玉雯, 宋佳, 黄盼娜, 张晓岚. 淋巴细胞归巢在炎症性肠病中的作用及相关治疗靶点[J]. 临床荟萃, 2025, 40(5): 468-472.