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Abstract

Objectives: We evaluated a continuous, immediate, localized ischemic preconditioning regimen in a rat model of ischemia-reperfusion injury and assessed whether it attenuated injury at the histologic and molecular levels. Materials and Methods: Fifteen adult male Lewis rats received sham operation, left unilateral warm ischemia (45 minutes of cross-clamping of the renal pedicle; ischemia-reperfusion injury group), or 15 minutes of ischemia followed by a 20-minute reperfusion period, 45 minutes of ischemiareperfusion injury, and subsequent reperfusion (ischemic preconditioning/ischemia-reperfusion injury group). Kidney tissue was retrieved 48 hours later, sectioned, stained with hematoxylin and eosin, and examined. We used RNA extraction and real-time quantitative polymerase chain reaction analysis to assess acute kidney injury markers, cytokines, and microRNA-21. Results: Forty-five minutes of unilateral ischemiareperfusion injury caused marked changes in histology at 48 hours, characterized by endothelial loss, tubulointerstitial damage (inflammation, cast formation), tubular cell necrosis, and glomerular capsule thickening. The ischemia-reperfusion injury and ischemic preconditioning/ischemia-reperfusion injury groups showed no measurable differences in histology. Expression of the acute kidney injury markers was significantly increased in the ischemiareperfusion injury versus Sham group; however, no difference was found between the ischemiareperfusion injury and ischemic preconditioning/ -ischemia-reperfusion injury groups. Similarly, expression of interleukin 17, interleukin 18, and tumor necrosis factor α was significantly increased in the ischemia-reperfusion injury versus Sham group. No significant difference was found between the ischemia-reperfusion injury and ischemic preconditioning/ischemia-reperfusion injury groups for interleukin 17 and interleukin 18; however, tumor necrosis factor α expression was significantly increased in the ischemic preconditioning/ischemiareperfusion injury versus ischemia-reperfusion injury group. Conclusions: In our ischemic preconditioning model, tumor necrosis factor α expression was increased without altering the sequelae of ischemia-reperfusion injury. The long-term consequences of this augmented early inflammatory response and whether these consequences are altered by variations in ischemic preconditioning or a subsequent injury require further study.