Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway.

Abstract

Purpose The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. Methods A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. Results RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. Conclusion SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.