The Protective Role of Sirt1 Activator in Renal Tubulointerstitial Fibrosis and Its Mechanism

Abstract: This study was designed to investigate the effects of the Sirt1 activator， SRT1720， on unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis and whether this effects depended on inhibition of oxidative stress and activation of TGF-β1/CTGF pathway in CD-1 mouse. Renal fibrosis was induced by UUO in CD-1 mice. The CD-1 mice were divided into Sham， UUO and SRT1720 groups. SRT1720 was administered. The change of histologic were examined by Masson’s trichrome stain. The expression of fibrosis-related factors were evaluated by Western blot and Real-time PCR. Apoptosis was examined by TUNEL. The study also examined superoxide dismutase (SOD)， malondialdehyde (MDA)， glutathione peroxidase (GPx) and reduced glutathione (GSH). SRT1720 increased Sirt1 levels and partially ameliorated renal interstitial fibrosis (RIF) and apoptosis induced by UUO. Furthermore， SRT1720 also attenuated the levels of oxidative stress， including SOD， MDA， GPx and GSH. Meanwhile， SRT1720 effectively inhibited TGF-β1/CTGF induced by UUO. These findings indicated that the Sirt1 activator， SRT1720， had protective effects on UUO-induced tubulointerstitial fibrosis. The mechanism of role performed by SRT1720 may include， at least in part suppressing renal oxidative stress and the TGF-β1/CTGF signalling pathway.

CSTR: 32200.14.cjcb.2015.08.0009