ROLE OF RENAL HEME OXYGENASE-1 IN RESPONSE TO ISCHEMIA/REPERFUSION IN RATS PRECONDITIONED BY HYPOXIA AND/OR REMOTE ISCHEMIA

摘要

Background: Heme oxygenase (HO) is the rate-limiting enzyme for heme degradation, and HO-1 is the inducible isoform. Induction of HO-1 is an adaptive response to injurious stimuli such as renal ischemia reperfusion (I/R). We examined the effect of preconditioning on response to renal I/R injury and the role of HO-1 in this response.Methods: Female Wistar rats were divided into four groups: sea level (SL, 1 atm = 101.3 kPa); hypoxic preconditioning (HA, 4 wks at 50.7 kPa); remote surgical ischemic preconditioning (SLR}; and preconditioning by hypoxia and remote surgical ischemia (HAR). Each group was randomized into control and renal I/R subgroups.Results: HO-1 protein expression and enzymatic activity was significantly higher in the HA, SLR, and HAR groups than in the SL group. ZnPP IX (HO inhibitor) was administered to assess changes in renal function, as determined by glomerular filtration rate (GFR) and renal blood flow. The renal function of rats undergoing I/R in the SLR, HA, and HAR groups were better than that of rats in the SL group.Conclusion: Renal preconditioning by hypoxia or a remote surgical procedure increased renal HO-1 expression and enzymatic activity. This appears to have a protective effect on the kidney in response to renal I/R injury.