Ozone oxidative pretreatment alleviates hypoxia/reoxygenation injury in renal tubular epithelial cells by regulating mitochondrial fission and fusion balance

ZHANG Jianwei; LI Shuqiang; MA Chao; SHI Lei; YUAN Pu; LIU Hao

doi:10.14188/j.1671-8852.2024.0003

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Ozone oxidative pretreatment alleviates hypoxia/reoxygenation injury in renal tubular epithelial cells by regulating mitochondrial fission and fusion balance

更新时间：2026-11-05

- Ozone oxidative pretreatment alleviates hypoxia/reoxygenation injury in renal tubular epithelial cells by regulating mitochondrial fission and fusion balance
- Medical Journal of Wuhan University Vol. 46, Issue 5, Pages: 600-605(2025)
- 作者机构：
  
  郑州大学第一附属医院泌尿外科河南郑州 450052
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0003
  CLC： R692.5
- Received：02 January 2024，
  
  Published：25 May 2025
- 稿件说明：
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张建伟,李书强,马超等.臭氧预处理通过调控线粒体裂变与融合平衡减轻肾小管上皮细胞缺氧/复氧损伤[J].武汉大学学报（医学版）,2025,46(05):600-605.

ZHANG Jianwei,LI Shuqiang,MA Chao,et al.Ozone oxidative pretreatment alleviates hypoxia/reoxygenation injury in renal tubular epithelial cells by regulating mitochondrial fission and fusion balance[J].Medical Journal of Wuhan University,2025,46(05):600-605.
张建伟,李书强,马超等.臭氧预处理通过调控线粒体裂变与融合平衡减轻肾小管上皮细胞缺氧/复氧损伤[J].武汉大学学报（医学版）,2025,46(05):600-605. DOI： 10.14188/j.1671-8852.2024.0003.

ZHANG Jianwei,LI Shuqiang,MA Chao,et al.Ozone oxidative pretreatment alleviates hypoxia/reoxygenation injury in renal tubular epithelial cells by regulating mitochondrial fission and fusion balance[J].Medical Journal of Wuhan University,2025,46(05):600-605. DOI： 10.14188/j.1671-8852.2024.0003.

摘要

目的

探究臭氧预处理对肾小管上皮HK2细胞缺氧/复氧损伤的作用及潜在机制。

方法

臭氧预处理HK2细胞后通过缺氧3 h复氧6 h建立缺氧/复氧损伤模型，TUNEL检测细胞凋亡；Western Blot检测Total⁃Drp1、p⁃Drp1 S616、p⁃Drp1 S637、MFN1/MFN2蛋白表达；分离细胞质和线粒体后，Western Blot检测Bax/Bcl2蛋白表达；Mito⁃Tracker染色后利用荧光共聚焦显微镜观察线粒体裂变与融合，并对线粒体数量和纵横比进行统计分析。

结果

臭氧预处理能够明显抑制缺氧/复氧过程细胞凋亡；抑制线粒体Bax蛋白表达并上调线粒体Bcl2蛋白表达。同时臭氧预处理抑制p⁃Drp1 S616蛋白表达，促进MFN1/MFN2蛋白表达；此外能够抑制线粒体裂变，促进线粒体融合。

结论

臭氧预处理能够减轻缺氧/复氧诱导的肾小管上皮细胞凋亡，其潜在机制可能是调控线粒体裂变与融合平衡。

Abstract

Objective

To investigate the effect and potential mechanism of ozone oxidative pretreatment (OzoneOP) on hypoxia/reoxygenation injury in renal tubular epithelial HK2 cells.

Methods

After HK2 cells were treated with OzoneOP

a hypoxia/reoxygenation injury model was established by hypoxia for 3 hours and reoxygenation for 6 hours. Apoptotic cells were measured by TUNEL; Western Blot was used to detect the expression of Total Drp1

p⁃Drp1 S616

p⁃Drp1 S637

and MFN1/MFN2 proteins. The cytoplasm and mitochondria were separated

and Bax/Bcl2 protein expression were detected by using Western Blot. Mito Tracker staining was used to observe mitochondrial fission and fusion under a fluorescence confocal microscope.

Results

OzoneOP inhibited cell apoptosis during hypoxia/reoxygenation processes

suppressed mitochondrial Bax protein expression

and upregulated mitochondrial Bcl2 protein expression. Moreover

ozone pretreatment inhibited the expression of p⁃Drp1 S616 protein and promoted the expression of MFN1/MFN2 protein; In addition

OzoneOP inhibited mitochondrial fission and promoted mitochondrial fusion.

Conclusion

OzoneOP can alleviate hypoxia/reoxygenation⁃induced apoptosis of renal tubular epithelial cells

and its potential mechanism may be to regulate mitochondrial fission and fusion balance.

关键词

Keywords

references

LERINK L J S , DE KOK M J C , MULVEY J F , et al . Preclinical models versus clinical renal ischemia reperfusion injury: A systematic review based on metabolic signatures [J ] . Am J Transplant , 2022 , 22 ( 2 ): 344 ⁃ 370 .

PABLA N , BAJWA A . Role of mitochondrial therapy for ischemic⁃reperfusion injury and acute kidney injury [J ] . Nephron , 2022 , 146 ( 3 ): 253 ⁃ 258 .

HUANG R , ZHANG C , XIANG Z , et al . Role of mitochondria in renal ischemia⁃reperfusion injury [J ] . FEBS J , 2024 , 17 ( 5 ): 14 ⁃ 18 .

CHEN Y , LI Z , ZHANG H , et al . Mitochondrial metabolism and targeted treatment strategies in ischemic⁃induced acute kidney injury [J ] . Cell Death Discov , 2024 , 10 ( 1 ): 69 .

GAO X , WU Y . Perioperative acute kidney injury: The renoprotective effect and mechanism of dexmedetomidine [J ] . Biochem Biophys Res Commun , 2024 , 695 : 149402 .

LACOMBE A , SCORRANO L . The interplay between mitochondrial dynamics and autophagy: From a key homeostatic mechanism to a driver of pathology [J ] . Semin Cell Dev Biol , 2024 , 161 ( 24 ): 1 ⁃ 19 .

CHO S G , XIAO X , WANG S X , et al . Bif⁃1 interacts with prohibitin⁃2 to regulate mitochondrial inner membrane during cell stress and apoptosis [J ] . J Am Soc Nephrol , 2019 , 30 ( 7 ): 1174 ⁃ 1191 .

JANDURA J , VAJDA M , CECH M , et al . Oxygen⁃ozone therapy of musculoskeletal neck pain: A review [J ] . J Pers Med , 2024 , 14 ( 3 ): 326 .

YANG H , WANG Z , ZHOU Y , et al . Association between long⁃term ozone exposure and readmission for chronic obstructive pulmonary disease exacerbation [J ] . Environ Pollut , 2024 , 348 ( 29 ): 123811 .

WANG R , LIU F J , HUANG P , et al . Ozone preconditioning protects rabbit heart against global ischemia⁃reperfusion injury in vitro by up⁃regulating HIF⁃1α [J ] . Biomed Pharmacother , 2022 , 150 : 113033 .

WANG Z W , ZHANG A , MENG W X , et al . Ozone protects the rat lung from ischemia⁃reperfusion injury by attenuating NLRP3⁃mediated inflammation, enhancing Nrf2 antioxidant activity and inhibiting apoptosis [J ] . Eur J Pharmacol , 2018 , 835 : 82 ⁃ 93 .

WANG L , CHEN Z Y , LIU Y , et al . Ozone oxidative postconditioning inhibits oxidative stress and apoptosis in renal ischemia and reperfusion injury through inhibition of MAPK signaling pathway [J ] . Drug Des Devel Ther , 2018 , 12 : 1293 ⁃ 1301 .

LIU K , LAN D F , LI C Y , et al . A double⁃edged sword: Role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury [J ] . Apoptosis , 2023 , 28( 3 ⁃ 4 ): 313 ⁃ 325 .

SCHMITT E , PAQUET C , BEAUCHEMIN M , et al . Characterization of Bax⁃sigma, a cell death⁃inducing isoform of Bax [J ] . Biochem Biophys Res Commun , 2000 , 270 ( 3 ): 868 ⁃ 879 .

EDLICH F , BANERJEE S , SUZUKI M , et al . Bcl⁃x(L) retrotranslocates bax from the mitochondria into the cytosol [J ] . Cell , 2011 , 145 ( 1 ): 104 ⁃ 116 .

LI J , WANG L , WANG B , et al . NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation [J ] . Theranostics , 2023 , 13 ( 9 ): 2863 ⁃ 2878 .

SONG Z , XIA Y , SHI L , et al . Inhibition of Drp1⁃Fis1 interaction alleviates aberrant mitochondrial fragmentation and acute kidney injury [J ] . Cell Mol Biol Lett , 2024 , 29 ( 1 ): 31 .

LIAO J Z , CHUNG H L , SHIH C , et al . Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila [J ] . Nat Commun , 2024 , 15 ( 1 ): 3326 .

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Related Institution

Department of Cardiology, Gucheng Hospital Affiliated to Hubei University of Arts and Science, Xiangyang

Department of Cardiology, Second Hospital of Tianjin Medical University & Tianjin Key Laboratory of Ionic‐Molecular Function of Cardiovascular Disease

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Department of Cardiology, Renmin Hospital of Wuhan University & Hubei Key Laboratory of Metabolic and Related Chronic Diseases

Department of Anesthesiology, Renmin Hospital of Wuhan University

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