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

Abstract
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 β type 1 (TGF-β1), α-smooth muscle actin (α-SMA), type I collagen (Col-I), and phosphorylated Smad2/3 (p-Smad2/3) was determined using immunohistochemistry. The protein expression levels of TGF-β1, α-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-β/Smad signalling pathways.
AuthorsXiao-hua Ning, Xiao-feng Ge, Yan Cui, Hui-xia An
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 15 Issue 2 Pg. 406-13 (Feb 2013) ISSN: 1878-1705 [Electronic] Netherlands
PMID23318600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Actins
  • Collagen Type I
  • Glycoproteins
  • Smad Proteins
  • Transforming Growth Factor beta
  • Trypsin Inhibitors
  • smooth muscle actin, rat
  • Creatinine
  • urinastatin
Topics
  • Actins (metabolism)
  • Animals
  • Blood Urea Nitrogen
  • Collagen Type I (metabolism)
  • Creatinine (blood)
  • Fibrosis
  • Glycoproteins (administration & dosage)
  • Kidney (drug effects, pathology)
  • Rats
  • Rats, Wistar
  • Signal Transduction (drug effects)
  • Smad Proteins (metabolism)
  • Transforming Growth Factor beta (metabolism)
  • Trypsin Inhibitors (administration & dosage)
  • Ureteral Obstruction (complications, pathology)

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