Effect of rapamycin on renal ischemia reperfusion injury

Abstract

Background: The aim of this study was to determine the effect of rapamycin (Rapa), a relatively new immunosuppressive drug, on renal ischemia reperfusion injury (IRI) in the mouse. Methods: Renal IRI was induced in male Balb/c mice by clamping both renal pedicles for 45 minutes. The mice were treated with either vehicle or Rapa (2 mg/kg/day) by oral gavage, starting 2 days before the IRI and continued daily until sacrifice. The mice were sacrificed at 1, 3, and 7 days after the operation. The severity of the 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). Results: One day after the IRI, the serum creatinine levels of Rapa-treated mice were significantly higher than those of vehicle-treated mice. Kidney sections from Rapa-treated mice also showed more marked tubular damage on day 1. The number of PCNApositive cells in Rapa-treated mice was significantly lower than that in vehicle-treated mice on days 1 and 3 after IRI. By day 7 after IRI, there was no significant difference between Rapa- and vehicle-treated mice in terms of serum creatinine levels, renal histology and positive PCNA staining. Conclusion: We conclude that Rapa treatment aggravates renal IRI during the first 1 to 3 days after the insult. This effect might be partly mediated through inhibition of renal tubular cell regeneration.