title: Fuzheng Huayu Formula () prevents rat renal interstitial fibrosis induced by HgCl2via antioxidative stress and down-regulation of nuclear factor-kappa B activity.
abstract: OBJECTIVE
  To investigate the mechanism of action of Fuzheng Huayu Formula (, FZHY) against renal interstitial fibrosis (RIF) relating to oxidative injury and nuclear factor-kappa B (NF-κB) activity.
  
  
  METHODS
  Thirty-two Sprague-Dawley rats were randomly divided into 3 groups: normal group, model group and FZHY treatment group. The RIF model was induced by oral administration of HgCl2at a dose of 8 mg/kg body weight once a day for 9 weeks. Meanwhile, rats in FZHY treatment group orally took FZHY at a dose of 4.0 g/kg rat weight for 9 weeks. The content of hydroxyproline (Hyp) and collagen deposition in kidney were observed. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of glutathione (GSH) and malondialdehyde (MDA) of kidney were tested. The expressions of inhibitor-κappa B (IκB), phospho-IκB (p-IκB), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) were analyzed by Western blot. α-SMA expression was also observed by immunofluorescent staining. MMP-2 activity was measured by gelatin zymography. NF-κB activation was determined by electrophoretic mobility shift assay.
  
  
  RESULTS
  Renal interstitial fibrosis was induced by HgCl2, demonstrated by remarkably increased Hyp contents and excessive collagen deposition in kidney (P<0.01). FZHY significantly inhibited renal interstitial collagen deposition and reduced Hyp content of the HgCl2-treated rats (P<0.01). GSH content decreased obviously, and MDA content increased signifificantly in HgCl2-treated rats compared with that of normal rats (P<0.01). FZHY significantly increased GSH content and decreased MDA content in the model rats (P<0.01). The expression α-SMA was increased in model rats compared with that of normal rats, FZHY signifificantly decreased its expression (P<0.01). The expressions of p-IκB and TNF-α and MMP-2, MMP-2 activity, and NF-κB activation were increased in model group compared with that in normal group (P<0.01), FZHY signifificantly decreased NF-κB activation, MMP-2 activity and p-IκB and TNF-α expressions (P<0.01).
  
  
  CONCLUSIONS
  FZHY could protect kidney from oxidative injury intoxicated by HgCl2, and antagonized oxidative stress-stimulated NF-κB activity through inhibition of IκB phosphorylation in the interstitial fibrotic kidney, these effects importantly contributed to FZHY action mechanism against renal interstitial fifibrosis.
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Ji-Li
authors.initials: JL
authors.lastname: Yuan
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tao
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Qing-Lan
authors.initials: QL
authors.lastname: Wang
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Chenghailiu@hotmail.com.|Shanghai Key Laboratory of Traditional, Chinese Clinical Medicine, Shanghai, 201203, China. Chenghailiu@hotmail.com.|E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai, 201203, China. Chenghailiu@hotmail.com.
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Liu
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005355:Fibrosis; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008627:Mercuric Chloride; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C532829:fuzheng huayu; D000072000:NF-KappaB Inhibitor alpha; D008315:Malondialdehyde; D008627:Mercuric Chloride; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D020778:Matrix Metalloproteinase 2; D005978:Glutathione
keywords: Chinese medicine; Fuzheng Huayu Formula; matrix metalloproteinase-2; mercuric chloride; nuclear factor-kappa B; oxidative stress; renal interstitial fifibrosis; tumor necrosis factor-α