title: [Role of the IGF-1/PI3K pathway and the molecular mechanism of Fuzhenghuayu therapy in a spontaneous recovery rat model of liver fibrosis].
abstract: OBJECTIVE
  To determine the role of IGF-1/PI3K pathway and investigate the molecular mechanism of Fuzhenghuayu (FZHY) therapy in a spontaneous recovery rat model of liver fibrosis.
  
  
  METHODS
  The liver fibrosis model was induced in male Wistar rats by administering 8 weeks of twice weekly CCL4 intraperitoneal injections without (untreated model) or with once daily FZHY (treated model). Normal, untreated rats served as the control group. At weeks 4, 6 and 8 (fibrosis) and 10, 12 and 14 (spontaneous recovery) after modeling initiation, effects on protein (a-SMA, IGF-1, PI3K) and mRNA (IGF-1, PI3K) expression levels were evaluated by immunohistochemistry and RT-PCR, respectively. Serum markers of liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and liver cell damage (alkaline hydrolysis, HYP) were measured. Histology was performed to assess the degree of inflammation and fibrosis (Ishak scoring system).
  
  
  RESULTS
  In the untreated model group, progression of liver fibrosis (weeks 4, 6 and 8) was accompanied by gradual increases in inflammation, necrosis, serum ALT and AST, and hepatic expression of a-SMA protein and IGF-1 and PI3K protein and mRNA; however, during the spontaneous recovery period (weeks 10, 12 and 14) the IGF-1 and PI3K protein and mRNA levels rapidly decreased and the HYP level, Ishak score, and a-SMA hepatic expression also decreased. The FZHY-treated model group showed significantly lower fibrosis-related up-regulation of IGF-1 and PI3K protein and mRNA expression, HYP level, Ishak score, and a-SMA hepatic expression at each time point (vs. untreated model group).
  
  
  CONCLUSIONS
  The IGF-1/PI3K pathway may contribute to progression of liver fibrosis. The mechanism by which FZHY prevents liver fibrosis in a rat model may involve blocking of the IGF/PI3K pathway and inhibiting HSC activation.
authors.affiliation: Traditional and Western Medical Department of Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Bo-rong
authors.initials: BR
authors.lastname: Wu
authors.forename: Yan-li
authors.initials: YL
authors.lastname: Zheng
authors.forename: Xian-liang
authors.initials: XL
authors.lastname: Sang
authors.forename: Meng
authors.initials: M
authors.lastname: Jin
authors.forename: Wei-zhen
authors.initials: WZ
authors.lastname: Wang
authors.forename: Qing-shan
authors.initials: QS
authors.lastname: Zhang
authors.forename: Su-xian
authors.initials: SX
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Kong
mesh_terms: D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases