title: Norcantharidin attenuates tubulointerstitial fibrosis in rat models with diabetic nephropathy.
abstract: OBJECTIVE
  To investigate the effects of norcantharidin (NCTD) on tubulointerstitial fibrosis of diabetic nephropathy (DN) in streptozotocin-induced rat model.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into control group, model group, low-dose NCTD (0.05 mg/kg/day) group, and high-dose NCTD (0.1 mg/kg/day) group. The model group was induced by injection intraperitoneally with 30 mg/kg streptozotocin in 0.1 mol/L sodium citrate solution (pH 4.5), after high-calorie foods were given for 2 months. NCTD was administered daily after the DN rat model was built. Rats were sacrificed at the end of the third and the eighth week; renal fibrosis and the expression of FN, collagen IV, TGF-β1, and calcineurin (CaN) were detected by Masson and immunohistochemistry staining, respectively.
  
  
  RESULTS
  Tubulointerstitial fibrosis was observed in DN rats, this kind of pathological changes was ameliorated in NCTD treatment group (p < 0.05). The expressions of FN, collagen IV, and TGF-β1 protein increased in the tubulointerstitial field of DN rats compared with the rats in control group. NCTD treatment could dose-dependently decrease their expression and reverse the fibrotic degree (p < 0.05). Meanwhile, the expression of CaN was detected in tubular fields of normal kidney and increased in the tubulointerstitial field in DN rats. However, NCTD downregulated its expression in a dose-dependent manner (p < 0.05).
  
  
  CONCLUSIONS
  NCTD could downregulate FN, collagen IV, and TGF-β1 expression in tubulointerstitial fields and attenuate tubulointerstitial fibrosis in the early stage of DN rats. NCTD also alleviated the expression of CaN in tubules in DN. The relationship between the role of NCTD's anti-tubulointerstitial fibrosis and its inhibition to CaN expression remains to be further elucidated.
authors.affiliation: Division of Nephrology, The Second Xiangya Hospital, Research Institute of Nephrology, Central South University, Changsha, PR China. liyingdoctor@yahoo.com.cn
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.forename: Fu-You
authors.initials: FY
authors.lastname: Liu
authors.forename: You-Ming
authors.initials: YM
authors.lastname: Peng
authors.forename: Tao
authors.initials: T
authors.lastname: Hou
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Duan
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Luo
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Ling
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D019703:Calcineurin / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D024141:Collagen Type IV; D005353:Fibronectins; D053773:Transforming Growth Factor beta1; C069741:norcantharidin; D003404:Creatinine; D019703:Calcineurin