Erythropoietin Ameliorates Renal Ischemia and Reperfusion Injury via Inhibiting Tubulointerstitial Inflammation

• Published in: The Journal of surgical research 2012-07, Vol.176 (1), p.260-266
• Main Authors: Hu, Linkun, M.D, Yang, Cheng, M.D, Zhao, Tian, M.D, Xu, Ming, Ph.D., M.D, Tang, Qunye, B.S, Yang, Bin, Ph.D, Rong, Ruiming, Ph.D., M.D, Zhu, Tongyu, Ph.D., M.D
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Creatinine - blood; Cytokines - metabolism; erythropoietin; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; inflammation; Kidney - blood supply; Kidney - metabolism; Kidney - pathology; Male; Models, Animal; Necrosis; Nephritis, Interstitial - metabolism; Nephritis, Interstitial - pathology; Nephritis, Interstitial - prevention & control; NF-kappa B - metabolism; NF-κB; Oxidative Stress - drug effects; Peroxidase - metabolism; Rats; Rats, Sprague-Dawley; renal ischemia-reperfusion injury; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2011.06.035

Background Tubulointerstitial inflammation is the characteristics of renal ischemia reperfusion injury (IRI) that is inevitable in kidney transplantation. Erythropoietin (EPO) has recently been shown to have protective effects on renal IRI by anti-apoptosis and anti-oxidation. Here, the effect and mechanism of EPO on renal IRI were further investigated, with a focus on tubulointerstitial inflammation. Materials and Methods Male Sprague-Dawley rats were administrated with saline or EPO prior to IRI induced by bilateral renal pedicle clamping. Twenty-four hours following reperfusion, the effects of EPO on renal IRI were assessed by renal function and structure, tubulointerstitial myeloperoxidase (MPO) positive neutrophils, and proinflammatory mediator gene expression. The translocation and activity of NF-κB in renal tissues were also evaluated. Results Compared with control groups, the EPO treated group exhibited lower serum urea and creatinine levels, limited tubular necrosis with a lower score of renal histological lesion. MPO positive cells in the tubulointerstitial area were greatly increased by IRI, but significantly reduced by the treatment of EPO. The gene expression of proinflammatory cytokines (IL-1β, IL-6, IL-10, and TNF-α) and chemokine (MCP-1) was also significantly decreased by EPO. In addition, less activation and nuclear-translocation of NF-κB was observed in the kidney treated by EPO as well. Conclusion EPO improved renal function and structure in IRI rats via reducing neutrophils in the tubulointerstitium, the production of proinflammatory cytokines and chemokine, as well as the activation and nuclear-translocation of NF-κB. EPO may have potential clinical applications as an anti-inflammation agent clinically for a wide range of injury.