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Updated: Jul 20, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Effect of rapamycin on renal ischemia-reperfusion injury in mice
Sing Leung Lui1, Kwok Wah Chan, Ryan Tsang
1Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. slliu@hku.hk
Abstract:
The aim of this study was to determine the effect of rapamycin on renal ischemia-reperfusion injury (IRI) in mice. Renal IRI was induced in male BALB/c mice by clamping both renal pedicles for 45 min. The mice were treated with either vehicle or rapamycin (2 mg/kg/day) by oral gavage, starting 1 day before the IRI and continued daily till killing. The mice were killed on days 1, 3 and 7 after the operation. The severity of the renal IRI was assessed by serum creatinine levels and renal histology. Proliferation of renal tubular cells was quantified by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). One day after the IRI, the serum creatinine levels of rapamycin-treated mice were significantly higher than those of the vehicle-treated mice. Kidney sections from rapamycin-treated mice showed more marked tubular damage and significantly lower number of PCNA-positive cells. The number of PCNA-positive cells in the rapamycin-treated mice remained significantly lower on day 3 after the IRI. By day 7 after the IRI, the serum creatinine levels, renal histology and positive PCNA staining in the kidney sections became similar between the two treatment groups. We conclude that in this murine model of renal IRI, rapamycin treatment aggravates renal IRI during the first 3 days after the insult. This effect might be mediated, at least partly, through inhibition of renal tubular cell proliferation.
Insights
Rapamycin treatment worsened kidney injury in mice after ischemia-reperfusion injury (IRI), likely by inhibiting renal tubular cell proliferation. Kidney function and damage markers normalized by day 7.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge.
- Rapamycin, an mTOR inhibitor, has immunomodulatory effects.
- The impact of rapamycin on renal IRI is not fully understood.
Purpose of the Study:
- To investigate the effect of rapamycin on renal IRI in a murine model.
- To assess the role of renal tubular cell proliferation in rapamycin-mediated effects.
Main Methods:
- Male BALB/c mice underwent 45-minute bilateral renal pedicle clamping to induce IRI.
- Mice received daily oral rapamycin (2 mg/kg) or vehicle starting one day pre-IRI.
- Renal function (serum creatinine), histology, and tubular cell proliferation (PCNA staining) were evaluated on days 1, 3, and 7 post-IRI.
Main Results:
- Rapamycin treatment significantly increased serum creatinine levels on day 1 post-IRI.
- More severe tubular damage and reduced PCNA-positive cells were observed in rapamycin-treated mice on days 1 and 3.
- By day 7, serum creatinine, histology, and PCNA staining were similar between groups.
Conclusions:
- Rapamycin exacerbates renal IRI in mice during the initial 3 days post-insult.
- Inhibition of renal tubular cell proliferation may contribute to rapamycin's detrimental effect on renal IRI.
- These findings suggest rapamycin's potential to worsen acute kidney injury in specific contexts.
