It has been reported that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) attenuates renal and cardiac inflammation as well as fibrosis in hypertensive rats. In this study, we investigated these effects using a unilateral ureteral obstruction (UUO) model. Eighteen male Wistar rats were randomly divided into three groups: control, UUO/vehicle and UUO/Ac-SDKP groups. Animal models of renal inflammation and tubulointerstitial fibrosis were established with unilateral ureteral ligation in rats. Ac-SDKP and vehicle were infused subcutaneously by using osmotic mini pumps for two weeks. On the 14th day post-injection, kidney histological changes of each group were observed by hematoxylin-eosin and Masson's stain. Renal macrophage infiltration, together with protein expression and localization of monocyte chemoattractant protein-1 (MCP-1), nuclear factor-kappa B (NF-κB), α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in renal tissue was assessed by immunohistochemical staining. Gene expression of MCP-1 and TGF-β1 was analyzed with reverse transcription-polymerase chain reaction. Ac-SDKP-treated animals demonstrated less severe renal inflammation and tubulointerstitial fibrosis. Interstitial fibrosis was significantly attenuated with Ac-SDKP. ED-1 was expressed in the interstitium of the UUO/vehicle group kidneys and decreased with Ac-SDKP treatment. MCP-1, NF-κB, α-SMA and TGF-β1 were increased in the renal interstitium and tubular epithelial cells of the UUO/vehicle group. Ac-SDKP significantly reduced their expressions. Gene expressions of MCP-1 and TGF-β1 were upregulated in the UUO/vehicle group kidneys and were significantly inhibited by Ac-SDKP. In conclusion, in the rat UUO model Ac-SDKP administration protected against renal inflammation and tubulointerstitial fibrosis. The inhibitory effect of Ac-SDKP was mediated by the reduction in the expression of MCP-1, NF-κB, α-SMA and TGF-β1.

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