[1]赵悦如,马善波,赵晋.急性肾损伤过程中肾小管上皮细胞的衰老机制与命运转归[J].陕西医学杂志,2025,54(10):1432-1435,封3.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.026]
 ZHAO Yueru,MA Shanbo,ZHAO Jin.Senescence Mechanisms and Fate Progression of Renal Tubular Epithelial Cells during AKI[J].,2025,54(10):1432-1435,封3.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.026]
点击复制

急性肾损伤过程中肾小管上皮细胞的衰老机制与命运转归

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年10期
页码:
1432-1435,封3
栏目:
综 述
出版日期:
2025-10-05

文章信息/Info

Title:
Senescence Mechanisms and Fate Progression of Renal Tubular Epithelial Cells during AKI
作者:
赵悦如12马善波3赵晋2
(1.西安交通大学医学部临床医学院,陕西 西安 710061;2.空军军医大学西京医院肾脏内科,陕西 西安 710032;3.空军军医大学西京医院药剂科,陕西 西安 710032)
Author(s):
ZHAO Yueru12MA Shanbo3ZHAO Jin2
(1.School of clinical medicine,Health Science Center,Xi’an Jiaotong University,Xi’an 710061,China;2.Department of Nephrology,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,China;3.Department of Pharmacy,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,China)
关键词:
急性肾损伤慢性肾脏病肾小管上皮细胞细胞衰老分泌表型铁死亡纤维化
Keywords:
Acute kidney injuryChronic kidney diseaseTubular epithelial cellCellular senescenceSecretory phenotypeFerroptosisFibrosis
分类号:
R 692
DOI:
DOI:10.3969/j.issn.1000-7377.2025.10.026
文献标志码:
A
摘要:
急性肾损伤(AKI)是临床常见的综合征,其核心病理特征为肾小管上皮细胞(TEC)的损伤与修复失衡。近年研究发现,TEC的衰老是AKI向慢性肾脏病(CKD)转化的关键机制之一。该文章结合国内外研究进展,系统阐述AKI过程中TEC衰老的分子机制及其命运转归,以期为干预策略提供理论依据。AKI过程中,TEC衰老涉及细胞周期停滞、DNA损伤、代谢重编程、铁死亡及分泌表型改变等多方面机制。其命运从早期的代偿性多倍体化逐步转向不可逆的纤维化与慢性炎症。通过比较早期和晚期衰老TEC的特征,深入理解其在AKI进展中的作用差异,对于制定精准治疗策略具有重要意义。
Abstract:
Acute kidney injury (AKI) is a common critical illness in clinical practice,characterized by damage and repair imbalance of renal tubular epithelial cells (TECs).Recent studies have shown that TEC senescence is a key mechanism in the progression of AKI to chronic kidney disease (CKD).TEC senescence involves multiple mechanisms,including cell cycle arrest,DNA damage,metabolic reprogramming,ferroptosis,and changes in secretory phenotype.The fate of TECs evolves from compensatory polyploidy in the early stage of AKI to irreversible fibrosis and chronic inflammation in the late stage.By comparing the characteristics of early and late senescent TECs and understanding their differential roles in AKI progression,we can better develop precise treatment strategies.

参考文献/References:

[1]曹斐斐,李屾森,李汶汶,等.慢性肾脏病并发急性肾损伤的危险因素及影响肾脏修复的机制研究进展[J].中国医药,2023,18(4):625-628.
[2]FERENBACH D A,BONVENTRE J V.Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD[J].Nat Rev Nephrol,2015,11(5):264-276.
[3]薛翔,李世军.急性肾损伤进展为慢性肾脏病的机制[J].肾脏病与透析肾移植杂志,2023,32(1):74-78.
[4]陈佳,何娅妮.肾小管细胞衰老在急性肾损伤中的研究进展[J].华西医学,2022,37(7):1076-1080.
[5]王诗涵,王顺.巨噬细胞极化对急性肾损伤向慢性肾脏病转换的作用[J].中国免疫学杂志,2024,40(12):2685-2690.
[6]LIN X,JIN H,CHAI Y,et al.Cellular senescence and acute kidney injury[J].Pediatr Nephrol,2022,37(12):3009-3018.
[7]敬梅,刘玉青,李翯,等.P16INK4a、IL-37和Cys-C联合检测在脓毒症急性肾损伤中的早期诊断价值[J].临床急诊杂志,2024,25(10):528-533.
[8]HARADA K,OGDEN G R.An overview of the cell cycle arrest protein,p21(WAF1)[J].Oral Oncol,2000,36(1):3-7.
[9]KRONENBERG F.Telomere length and chronic kidney disease:Cause or consequence?[J].Kidney Int,2021,100(5):980-983.
[10]KESHAWARZ A,JOEHANES R,MA J,et al.Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis[J].Epigenetics,2023,18(1):2211361.
[11]方顺金,周洁,沈健.危重症急性肾损伤患者血清炎症因子与抢救结局的相关性[J].中国急救医学,2025,45(3):226-231.
[12]彭斌,冯雪,冯立,等.益肾排毒方调节TGF-β1/smads信号通路对慢性肾衰竭大鼠肾间质纤维化的影响[J].中国老年学杂志,2025,45(9):2196-2201.
[13]杨欣欣,吴珊珊,马俊杰,等.免疫细胞亚群在顺铂肾毒性中的作用研究进展[J].中国现代应用药学,2024,41(20):2884-2894.
[14]王佳慧,郑可,李雪梅.脂质组学在肾脏疾病中的应用与进展[J].实用医学杂志,2025,41(1):1-6.
[15]秦炜宏,杨萌,刘新光.糖代谢重塑与慢性肾脏病[J].生命的化学,2025,45(3):407-417.
[16]刘颖,孟超,赵谊,等.自噬蛋白Beclin1及炎症因子表达在脓毒症急性肾损伤中的作用[J].中华危重症医学杂志:电子版,2020,13(6):401-405.
[17]洪佳,陈勇.自噬与糖尿病肾病的关系及中医药干预机制研究进展[J].陕西中医,2024,45(4):574-577.
[18]丁文庆,马洪闯,罗群.铁死亡在急性肾损伤进展为慢性肾脏病中的作用[J].肾脏病与透析肾移植杂志,2024,33(4):356-361.
[19]XU D,JIANG J,LIU Y,et al.TIMP2 protects against sepsis-associated acute kidney injury by cAMP/NLRP3 axis-mediated pyroptosis[J].Am J Physiol Cell Physiol,2024,326(5):c1353-c1366.
[20]倪曼,葛郡,孔子昂.HMGB1、MCP-1水平与脓毒症合并AKI患者预后的相关性[J].天津医药,2025,53(3):297-301.
[21]TECKLENBORG J,CLAYTON D,SIEBERT S,et al.The role of the immune system in kidney disease[J].Clin Exp Immunol,2018,192(2):142-150.
[22]蒲叶凡,王嘉旺,范军.糖尿病肾病中细胞衰老与纤维化生态位的联系[J].肾脏病与透析肾移植杂志,2025,34(2):163-167.
[23]董礼,陈晓婷,张辉,等.基于SIRT1/TGF-β1/Smad通路研究健脾固肾化瘀方治疗糖尿病肾病机制[J].天津中医药大学学报,2024,43(7):625-631.
[24]DE CHIARA L,ROMAGNANI P.Polyploid tubular cells and chronic kidney disease[J].Kidney Int,2022,102(5):959-961.
[25]张凌晗,刘金英,王润秀,等.上皮间质转化的调控机制及其在肾纤维化中作用的研究进展[J].赣南医学院学报,2024,44(6):634-640.
[26]MOLDOVEANU T,CZABOTAR P E.BAX,BAK and BOK:A coming of age for the BCL-2 family effector proteins[J].Cold Spring Harb Perspect Biol,2020,12(4):a036319.
[27]张钦媛,陈彦旭,秦大凯,等.中药调控Nrf2信号通路干预糖尿病肾病研究进展[J].中国实验方剂学杂志,2025,31(1):1-14.
[28]YAO
[29]LEE H,FESSLER M B,QU P,et al.Macrophage polarization in innate immune responses contributing to pathogenesis of chronic kidney disease[J].BMC Nephrol,2020,21(1):270.
[30]DELLEPIANE S,LEVENTHAL J S,CRAVEDI P.T Cells and acute kidney injury:A two-way relationship[J].Front Immunol,2020,11:1546.
[31]庞浩文,安宁,杨陈,等.Th17细胞及IL-17在急性肾损伤中作用的研究进展[J].临床肾脏病杂志,2021,21(11):944-950.
[32]MOORE K H,AGARWAL A.The Importance of Immune Checkpoint Molecule TIGIT in AKI[J].J Am Soc Nephrol,2023,34(5):725-727.
[33]陈鑫,胡卿源,宋智慧.程序性死亡受体1抑制剂相关急性肾损伤的临床特征及影响因素[J].临床药物治疗杂志,2025,23(02):39-44.
[34]黎艳,刘莉,王琪文,等.槲皮素对小鼠单侧输尿管结扎致肾间质纤维化的改善作用及机制研究[J].陕西医学杂志,2023,52(11):1473-1477,82.
[35]晏青,程芝梅,张帅,等.吡非尼酮对肾纤维化大鼠的治疗作用及分子机制[J].贵州医科大学学报,2024,49(3):354-360.
[36]ONG C H,THAM C L,HARITH H H,et al.TGF-β-induced fibrosis:A review on the underlying mechanism and potential therapeutic strategies[J].Eur J Pharmacol,2021,911:174510.
[37]HE S,GAO Q,WU X,et al.NAD(+) ameliorates endotoxin-induced acute kidney injury in a sirtuin1-dependent manner via GSK-3β/Nrf2 signalling pathway[J].J Cell Mol Med,2022,26(7):1979-1793.W,CHEN Y,LI Z,et al.Single cell RNA sequencing identifies a unique inflammatory macrophage subset as a druggable target for alleviating acute kidney injury[J].Adv Sci (Weinh),2022,9(12):e2103675.

相似文献/References:

[1]杨 雄,高 伟,邱万胜,等.白蛋白球蛋白比值对慢性肾脏病患者预后判断的价值研究[J].陕西医学杂志,2020,49(6):728.[doi:DOI:10.3969/j.issn.10007377.2020.06.022]
[2]张 星,高 明,赵 武,等.微小RNA-21对急性肾损伤模型大鼠线粒体氧化磷酸化的影响及机制研究[J].陕西医学杂志,2022,51(3):274.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.003]
 ZHANG Xing,GAO Ming,ZHAO Wu,et al.Effect of microRNA-21 on oxidative phosphorylation of mitochondria in rats with acute renal injury and its mechanism[J].,2022,51(10):274.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.003]
[3]王 萍,王文娟,杜 翔.慢性肾脏病患者肾素-血管紧张素系统与血浆β-淀粉样蛋白相关性研究[J].陕西医学杂志,2022,51(5):574.[doi:DOI:10.3969/j.issn.1000-7377.2022.05.014]
 WANG Ping,WANG Wenjuan,DU Xiang.Correlation between renin-angiotensin system and plasma beta-amyloid peptide in patients with chronic kidney disease and its significance[J].,2022,51(10):574.[doi:DOI:10.3969/j.issn.1000-7377.2022.05.014]
[4]谢琼燕,许环清,叶 文,等.生物标志物预测脓毒症引发急性肾损伤临床研究[J].陕西医学杂志,2023,52(7):880.[doi:DOI:10.3969/j.issn.1000-7377.2023.07.024]
 XIE Qiongyan,XU Huanqing,YE Wen,et al.Clinical study of using biomarkers to predict acute kidney injury induced by sepsis[J].,2023,52(10):880.[doi:DOI:10.3969/j.issn.1000-7377.2023.07.024]
[5]李梦梦,张淑英,赵艳杰.视黄醇结合蛋白、胱抑素C、胃泌素前体释放肽水平联合超微血流成像在慢性肾脏病诊断中的价值研究[J].陕西医学杂志,2024,(4):483.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.010]
 LI Mengmeng,ZHANG Shuying,ZHAO Yanjie.Diagnostic value of RBP,CysC and proGRP in combination with superb micro-vascular imaging in chronic kidney disease[J].,2024,(10):483.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.010]
[6]方修移,吴小冬,潘美娟,等.罗沙司他治疗慢性肾脏病合并肾性贫血临床价值研究[J].陕西医学杂志,2024,(5):666.[doi:DOI:10.3969/j.issn.1000-7377.2024.05.020]
 FANG Xiuyi,WU Xiaodong,PAN Meijuan,et al.Value of roxadustat in the treatment of chronic kidney disease complicated with renal anemia[J].,2024,(10):666.[doi:DOI:10.3969/j.issn.1000-7377.2024.05.020]

备注/Memo

备注/Memo:
国家自然科学基金资助面上项目(82470735)
更新日期/Last Update: 2025-10-09