Role of SIRT1 in renal ischemia-reperfusion injury and its effect on NF-κBp65 - PGC-1α signal pathway in mice

Abstract

Objective To investigate the role of silent mating type information regulation 2 homologue 1(SIRT1) in renal ischemia-reperfusion(IR) injury and its effect on NF-κBp65 - peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) signal pathway in mice. Methods Seventy-two healthy C57BL/6 male mice were randomly divided into four groups: control group(n=18), sham-operated group(n=18), IR group(n=18), resveratrol group(n=18). Bilateral renal pedicle were clamped for 45 min was adopted to establish the model of acute ischemic renal injury, to give 2% dimethyl sulfoxide or resveratrol by intraperitoneal injection for 7 days before modeling. Determination techniques included routine biochemical methods for the the levels of Scr and BUN, spectrophotometry for the level of superoxide dismutase (SOD), HE staining for the histological changes as well as immunohistochemical method and Western blotting for the expressions of SIRT1, NF-κBp65 and PGC-1α, respectively. Results Compared with that in control and sham-operated groups, the levels of serum Scr and BUN were higher and SOD levels in renal tissues were lower at 12 h and 24 h after operation in IR groups(P<0.05). HE staining revealed evident pathological lesions including necrosis of renal tubular epithelial cells in IR group. Compared with that in IR group, resveratrol attenuated the above-mentioned changes. Western blotting revealed the up-regulated SIRT1 expression and the activated NF-κB signal pathway, the up-regulated p65 expression and the down-regulated PGC-1α expression subsequent to IR(P<0.05). Both Western blotting and immunohistochemistry showed that the expressions of SIRT1 and PGC-1α in resveratrol group were up-regulated compared to that in IR group(P<0.05), while the NF-κBp65 expression in resveratrol group was down-regulated(P<0.05). Conclusions In mouse model of renal ischemia-reperfusion injury, the activation of SIRT1 can inhibit the NF-κBp65 expression and accordingly up-regulated PGC-1α level, contributing to inhibiting inflammatory reactions and attenuating oxidative stress-induced injury in the protection of the kidneys. Key words: Reperfusion injury; Oxidative stress; Inflammation; SIRT1; Resveratrol