title: Inhibitory effects of rapamycin on the different stages of hepatic fibrosis.
abstract: OBJECTIVE
  To investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis.
  
  
  METHODS
  We performed bile duct ligation (BDL) in male Wistar rats (n = 24). The experimental rats were classified into four groups: the BDL(+)/Rapa(-) group (un-treated control, n = 4), the BDL(+)/Rapa(+) group (treated 14 d after BDL, n = 8), the BDL(+)/Rapa(++) group (treated on the day after BDL, n = 8), and the BDL(-)/Rapa(-) group (un-treated, sham -operated control, n = 4). The BDL(+)/Rapa(+) and BDL(+)/Rapa(++) groups were administered rapamycin (2 mg/kg) for 28 d. The liver tissues were tested by immunohistochemical staining for α-smooth muscle actin (α-SMA) and cytokeratin.
  
  
  RESULTS
  The liver mRNA levels of transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were measured using the polymerase chain reaction. The protein levels of liver p70s6K and p-p70s6k were determined using Western blotting. α-SMA expression was lowest in the BDL(+)/Rapa(++)group. TGF-β1 and PDGF expression levels in the rapamycin-treated group were lower than those in the un-treated group and higher than those in the control groups (TGF-β1: 0.23 ± 0.00 vs 0.34 ± 0.01, 0.23 ± 0.0 vs 0.09 ± 0.00, P < 0.0001; PDGF: 0.21 ± 0.00 vs 0.34 ± 0.01, 0.21 ± 0.0 vs 0.09 ± 0.00, P < 0.0001). The p70s6k and p-p70s6k levels decreased in the treated groups and were lowest in the BDL(+)/Rapa(++)group (p70s6k: 1.05 ± 0.17 vs 1.30 ± 0.56, 0.40 ± 0.01 vs 1.30 ± 0.56, P < 0.0001; p-p70s6k: 1.40 ± 0.5 vs 1.67 ± 0.12, 0.70 ± 0.01 vs 1.67 ± 0.12, P < 0.0001).
  
  
  CONCLUSIONS
  The results of our study indicate that rapamycin has inhibitory effects on liver fibrosis, and the treatment is most effective in the early stages of fibrosis.
authors: Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors: Yun Jeung
authors: YJ
authors: Kim
authors: Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors: Eaum Seok
authors: ES
authors: Lee
authors: Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors: Seok Hyun
authors: SH
authors: Kim
authors: Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors: Heon Young
authors: HY
authors: Lee
authors: Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors: Seung Moo
authors: SM
authors: Noh
authors: Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors: Dae Young
authors: DY
authors: Kang
authors: Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors: Byung Seok
authors: BS
authors: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus
keywords: Liver cirrhosis; Platelet-derived growth factor; Ribosomal protein S6 kinases; Sirolimus; Transforming growth factor beta