Pancreatic kininogenase protects against renal fibrosis in rat model of unilateral ureteral obstruction

AIM To assess the beneficial effects of pancreatic kininogenase （PK） on renal fibrosis in rat model of unilateral ureteral obstruction （UUO）. METHODS Male Sprague-Dawley rats were randomly assigned to 5 groups and treated daily with PK for 7 d and 14 d. Masson trichrome and HE staining were used to assess the degree of tubulointerstitial fibrosis， and immunohistochemistry and Western blot were employed to evaluate the expression of profibrotic and proinflammatory cytokines， and apoptosis- and autophagy-related proteins. RESULTS PK treatment significantly decreased expression of profibrotic and proinflammatory cytokines， and these were paralleled with attenuation of tubulointerstitial inflammation ［monocyte chemoattractant protein-1 （MCP-1） and Toll-like receptor 2 （TLR-2）］ and fibrosis ［transforming growth factor β1 （TGF-β1） and connective tissue growth factor （CTGF）］ in a time-dependent manner. Oxidative stress induced by UUO manifested by augment of oxidant enzymes ［NADPH oxidase-2 （NOX-2） and NOX-4］ and decrease in antioxidant enzymes ［superoxide dismutase 1 （SOD1） and SOD2］， which was closely associated with dysregulation of apoptosis- and autophagy-related proteins subsequent excessive apoptotic （Bcl-2/Bax and cleaved caspase-3） and autophagy （LC3B， beclin-1 and P62）， and all of these were eliminated by administration of PK. CONCLUSION PK treatment protects against the progression of renal fibrosis in obstructed kidneys probably by interfering oxidative stress and programmed cell death.