title: [Effect of urokinase on renal interstitial inflammation in rats with chronic cyclosporine A nephropathy and its possible mechanism].
abstract: OBJECTIVE
  To investigate the protective effect of urokinase on renal interstitial inflammation and fibrosis in rats with chronic cyclosporine A (CsA)-induced nephropathy.
  
  
  METHODS
  Male SD rats were fed on low salt diet (0.05% sodium) for 7 days and randomized into 4 groups for treatment with CsA, CsA+continuous low-dose uPA (U2), intermittent CsA+ high-dose uPA (U6) or vehicle (control group). In the former 3 groups, the rats were subjected to daily intragastric administration of CsA (25 mg/kg) for 4 weeks to establish CsA-induced chronic nephropathy model, and those in U2 and U6 groups were given uPA at 2000 U/kg daily or at 6000 U/kg every 3 days, respectively. Four weeks after the treatment, the renal function and 24-h proteinuria were assessed, and Masson staining was used for examining fibrin deposition. Semi-quantitative immunohistochemical staining was employed for evaluation of ED-1-positive cells, urokinase-type plasminogen activator (uPA) and transforming growth factor-beta1 (TGF-beta 1).
  
  
  RESULTS
  Four weeks after the treatment, the CsA-treated rats showed significantly elevated serum creatinine (Scr), blood urea nitrogen (BUN) and increased urine proteins. Continuous administration of low-dose uPA resulted in significantly reduced Scr, BUN and 24-h urine protein excretion, while intermittent high-dose uPA treatment did not produce such changes. CsA increased fibrin deposition, total number of macrophages in renal interstitium and TGF-beta1 expression in the renal tissue, which were significantly reduced in U2 group (P<0.05) but not in U6 group (P>0.05).
  
  
  CONCLUSIONS
  Continuous administration of low-dose uPA may reduce interstitial fibrin deposition and alleviate renal interstitial inflammation in rats with chronic CsA nephropathy, possibly by reducing the number of macrophages and TGF-beta1 expression in the renal tissue.
authors.affiliation: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China. yinwang138@126.com
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Jun-rong
authors.initials: JR
authors.lastname: Tong
authors.forename: Zheng-mao
authors.initials: ZM
authors.lastname: Luo
authors.forename: Feng
authors.initials: F
authors.lastname: He
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009393:Nephritis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D014568:Urokinase-Type Plasminogen Activator