Remote ischemic preconditioning protects the kidney against injury after ischemia and reperfusion through activation of hypoxia-inducible factor 1

Clinical studies suggest that remote ischemic preconditioning (RIPC) in the arm or leg may protect the heart, brain and kidney against injury after ischemia and reperfusion. However, the detailed mechanism remains unclear. A recent study indicates that Hypoxia-Inducible Factor 1 (HIF-1) activates IL-10 gene transcription and is required for remote ischemic preconditioning of the heart. In this study, we investigate the role of HIF-1 in the protection effect of RIPC in the kidney after ischemia and reperfusion injury (IRI). RIPC was induced by blocking unilateral femoral artery for 5 min followed by 5 min of reperfusion for a total of five cycles. IRI was induced by blocking bilateral renal artery for 45 min followed by 120 min of reperfusion. The HIF specific inhibitor YC-1 was injected through tail vein with the dose of 2 mg/kg before surgery operation. Results showed that renal functions including serum creatinine, cystatin C and tubular injury score after IRI in rats with RIPC pretreatment were significantly better than in those without RIPC treatment. Renal expression of SOD and p-AKT were also elevated after RIPC. Our study also showed that RIPC treatment itself obviously induced the accumulation of HIF-1 in rat renal tubular epithelial nucleus and further induced upregulation of mRNA levels of target genes of HIF, such as EPO, VEGF and HO-1. Taken together, these data indicate that the protective effect of RIPC against IRI might be achieved through the activation of HIF.