title: Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat model of unilateral ureteral obstruction.
abstract: OBJECTIVE
  The purpose of this study was to explore effects of rapamycin on renal hypoxia, interstitial inflammation and fibrosis, and the expression of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO).
  
  
  METHODS
  Male Sprague-Dawley rats (n=36) were randomly divided into three groups (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and 24-h urine protein levels were measured. The extent of interstitial fibrosis was determined by Masson's trichrome staining. ED-1 positive macrophages, type III collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions were detected using immunohistochemical staining, real-time PCR and Western blot.
  
  
  RESULTS
  UUO induced an elevation in Scr, renal hypoxia, inflammation, interstitial fibrosis, TGF-β1, VEGF, Flk-1, and Flt-1 mRNA and protein expression levels (P < 0.05). Rapamycin alleviated the UUO-induced renal hypoxia, infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and 7). Rapamycin also down-regulated the UUO-induced elevated expression levels of TGF-β1 and Flt-1 mRNA and protein (P < 0.05). Rapamycin decreased VEGF mRNA and protein expression at day 3, and increased Flk-1 mRNA and protein expression at day 7, compared with the UUO group (P < 0.05).
  
  
  CONCLUSIONS
  Rapamycin shows beneficial effects by reducing UUO-induced renal hypoxia, inflammation and tubulointerstitial fibrosis.
authors.forename: Chun-feng
authors.initials: CF
authors.lastname: Liu
authors.forename: Hing
authors.initials: H
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Su-hua
authors.initials: SH
authors.lastname: Jiang
authors.forename: Jia-ming
authors.initials: JM
authors.lastname: Zhu
authors.affiliation: . ding.xiaoqiang@zs-hospital.sh.cn.
authors.forename: Xiao-qiang
authors.initials: XQ
authors.lastname: Ding
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005355:Fibrosis / Q000188:drug therapy* / Q000209:etiology; D000860:Hypoxia / Q000188:drug therapy* / Q000209:etiology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020123:Sirolimus / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014517:Ureteral Obstruction / Q000150:complications*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
chemical_list: D053773:Transforming Growth Factor beta1; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D020123:Sirolimus