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Updated: May 8, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Postconditioning ameliorates mitochondrial DNA damage and deletion after renal ischemic injury
Xiaohua Tan1, Lei Zhang, Yunpeng Jiang
1Department of Pathology, Norman Bethune School of Medicine, Jilin University, Jilin, China.
Background:
Reactive oxygen species (ROS) play a major role in causing injury in ischemia-reperfusion (I/R). Mitochondrial DNA (mtDNA) is particularly vulnerable to oxidative damage. We propose that increased mitochondrial ROS production is likely to damage mtDNA, causing further injury to mitochondria, and postconditioning (POC) may ameliorate kidney I/R injury by mitigating mitochondrial damage.
Methods:
Rats were divided into seven groups: (i) Sham-operated animals with an unconstricted renal artery; (ii) Sham + 5-hydroxydecanoate (5-HD); (iii) I/R; (iv) I/R + 5-HD; (v) POC; (vi) Sham POC and (vii) POC + 5-HD. Renal injury, oxidative DNA damage, mtDNA deletions, mitochondrial membrane potential (MMP) and expression of the ATP-sensitive K(+) (KATP) channel subunit Kir6.2 were evaluated.
Results:
Following 1 h of reperfusion, animals in the I/R group exhibited increased ROS, oxidative mtDNA damage shown by 8-hydroxy-2-deoxyguanosine staining, multiple base pair deletions and decreased MMP. However, POC rats exhibited less ROS, oxidative mtDNA damage and deletions and improved MMP. After 2 days of reperfusion, serum creatinine was elevated in I/R rats and the number of TdT-mediated dUTP nick-end labeled-positive tubular cells was increased and was associated with activation of caspase-3. Therefore, POC prevented the deleterious effects of I/R injury. Furthermore, the expression of mitochondrial Kir6.2 was widely distributed in renal tubular epithelial cells in Sham and POC rats and was lower in I/R rats. All of the protective effects of POC were reversed by the K(+) (KATP) channel blocker 5-HD.
Conclusion:
POC may attenuate I/R injury by reducing mitochondrial oxidative stress and mtDNA damage and sustaining MMP.
Insights
Postconditioning (POC) protects kidneys from ischemia-reperfusion (I/R) injury by reducing mitochondrial reactive oxygen species (ROS) and DNA damage. This protective effect is mediated by ATP-sensitive potassium (KATP) channels.
Area of Science:
- Mitochondrial biology
- Renal pathophysiology
- Oxidative stress research
Background:
- Ischemia-reperfusion (I/R) injury significantly involves reactive oxygen species (ROS) and subsequent mitochondrial damage.
- Mitochondrial DNA (mtDNA) is highly susceptible to oxidative damage, exacerbating cellular injury.
- Postconditioning (POC) is investigated as a potential therapeutic strategy to mitigate I/R-induced kidney damage.
Purpose of the Study:
- To investigate the role of mitochondrial ROS and mtDNA damage in kidney I/R injury.
- To determine if POC can attenuate kidney I/R injury by preserving mitochondrial integrity.
- To explore the involvement of ATP-sensitive potassium (KATP) channels in POC's protective mechanism.
Main Methods:
- Rats underwent sham operation or I/R, with or without POC and the KATP channel blocker 5-hydroxydecanoate (5-HD).
- Evaluated renal injury, oxidative DNA damage (8-hydroxy-2-deoxyguanosine), mtDNA deletions, mitochondrial membrane potential (MMP), and Kir6.2 expression.
- Assessed serum creatinine and caspase-3 activation to quantify tubular injury.
Main Results:
- I/R induced increased ROS, mtDNA damage, deletions, and decreased MMP, alongside elevated serum creatinine and caspase-3 activation.
- POC significantly reduced ROS, oxidative mtDNA damage, and preserved MMP, thereby preventing I/R-induced kidney injury.
- The protective effects of POC were abolished by 5-HD, indicating the crucial role of KATP channels.
Conclusions:
- POC attenuates kidney I/R injury by reducing mitochondrial oxidative stress and mtDNA damage.
- Sustaining mitochondrial membrane potential is a key mechanism in POC's renoprotective effect.
- KATP channel activation is essential for the beneficial outcomes of POC in I/R injury.
