論文

査読有り
2016年8月1日

Antifibrotic effects of ambrisentan, an endothelin-A receptor antagonist, in a non-alcoholic steatohepatitis mouse model

World Journal of Hepatology
  • Toshiaki Okamoto
  • Masahiko Koda
  • Kennichi Miyoshi
  • Takumi Onoyama
  • Manabu Kishina
  • Tomomitsu Matono
  • Takaaki Sugihara
  • Keiko Hosho
  • Junichi Okano
  • Hajime Isomoto
  • Yoshikazu Murawaki
  • 全て表示

8
22
開始ページ
933
終了ページ
941
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.4254/wjh.v8.i22.933
出版者・発行元
Baishideng Publishing Group Co

AIM: To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse model. METHODS: Fatty liver shionogi (FLS) FLS-ob/ob mice (male, 12 wk old) received ambrisentan (2.5 mg/kg orally per day
n = 8) or water as a control (n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the liver. RESULTS: In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group (18.0 μg/g ± 6.1 μg/g vs 33.9 μg/g ± 13.5 μg/g liver, respectively, P = 0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, were also significantly lower in the ambrisentan group (0.46% ± 0.18% vs 1.11% ± 0.28%, respectively, P = 0.0003
and 0.12% ± 0.08% vs 0.25% ± 0.11%, respectively, P = 0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were significantly lower by 60% and 45%, respectively, in the ambrisentan group. Inflammation, steatosis, and endothelin-related mRNA expression in the liver were not significantly different between the groups. CONCLUSION: Ambrisentan attenuated the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.

リンク情報
DOI
https://doi.org/10.4254/wjh.v8.i22.933
ID情報
  • DOI : 10.4254/wjh.v8.i22.933
  • ISSN : 1948-5182
  • SCOPUS ID : 84988358382

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