Ulinastatin inhibits unilateral ureteral obstruction-induced renal interstitial fibrosis in rats via transforming growth factor β (TGF-β)/Smad signalling pathways

This study aims to explore the protective effects and mechanisms of ulinastatin (UTI), which is a urinary trypsin inhibitor, of the renal interstitial fibrosis of rats subjected to unilateral ureteral obstruction (UUO). A total of 36 male Wistar rats were divided in random into three groups, namely, the sham operation (SOR) group (n = 12), the UUO group (n = 12), and the UTI treatment group (n = 12). Six rats from each group were euthanised after unilateral ureteral obstruction operation on the seventh and fourteenth days, respectively. Blood samples were harvested for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement. The interstitial pathological changes of the tissue from the obstructed kidneys were observed using haematoxylin-eosin (H&E) and Masson staining. The expression of the transforming growth factor beta type 1 (TGF-beta 1), alpha-smooth muscle actin (alpha-SMA), type I collagen (Col-I), and phosphorylated Smad2/3 (p-Smad2/3) was determined using immunohistochemistry. The protein expression levels of TGF-beta 1, alpha-SMA, and p-Smad2/3 were examined using Western blot analysis. The results show that ulinastatin has no statistically significant effect on the BUN and Scr levels (P>0.05), but it can significantly reduce renal interstitial injury and suppress interstitial collagen deposits. The renoprotective effect of ulinastatin is likely realised through the TGF-beta/Smad signalling pathways. (C) 2013 Elsevier B.V. All rights reserved.