title: Berberine ameliorates renal interstitial fibrosis induced by unilateral ureteral obstruction in rats.
abstract: OBJECTIVE
  To investigate the potential effects of berberine on renal interstitial fibrosis (RIF) of obstructed kidneys in a unilateral ureteral obstruction (UUO) rat model.
  
  
  METHODS
  Forty-eight rats were randomly divided into three groups: sham-operated, vehicle-treated UUO, and berberine-treated UUO. Rats were gavaged with berberine (200 mg/kg per day) or vehicle. Eight randomly chosen rats in each group were kiled and specimens were collected at day 14 after UUO. Physiological parameters and histological changes were assessed, RIF was evaluated using Masson's trichrome and Sirius red staining, oxidative stress and inflammation markers were determined, transforming growth factor β1 (TGF-β1), phosphorylated Smad3 (pSmad3) and α-smooth muscle actin (α-SMA) were measured using immunohistochemistry or western blotting analysis. The obstruction was relieved at day 14 by percutaneous nephrostomy in the remaining UUO rats. The resistive index of left kidneys was undertaken by coloured Doppler flow imaging at day 14 before nephrostomy and day 7 after the relief.
  
  
  RESULTS
  Berberine treatment significantly attenuated RIF induced by UUO. The UUO-induced reduction in kidney superoxide dismutase and catalase activities increased, whereas elevated kidney malondialdehyde level markedly decreased. Berberine treatment significantly ameliorated UUO-induced inflammation, and decreased TGF-β1, pSmad3 and α-SMA expression of UUO kidneys. Moreover, berberine treatment significantly suppressed the increase of resistive index compared with UUO group at day 14 after UUO as well as day 7 after the relief of obstruction.
  
  
  CONCLUSIONS
  Berberine treatment ameliorates RIF in a UUO rat model by inhibition of oxidative stress, inflammatory responses, and TGF-β1/pSmad3 signalling.
authors.affiliation: Department of Urology, Peking University Third Hospital, Beijing, China.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Wang
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Yang
authors.forename: Lu-Lin
authors.initials: LL
authors.lastname: Ma
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Tian
authors.forename: Ya-Qiang
authors.initials: YQ
authors.lastname: He
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D006869:Hydronephrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D064804:Urological Agents / Q000494:pharmacology*
chemical_list: D000199:Actins; D001599:Berberine; D015415:Biomarkers; D002374:Catalase; D018836:Inflammation Mediators; D008315:Malondialdehyde; D051900:Smad3 Protein; D013482:Superoxide Dismutase; D053773:Transforming Growth Factor beta1; D064804:Urological Agents; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat
keywords: berberine; fibrosis; oxidative stress; rats; ureteral obstruction