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2007 Fiscal Year Annual Research Report

非アルコール性脂肪性肝炎の発症・進展メカニズムの分子病理学的解析と予防的治療戦略

Research Project

Project/Area Number 18590324
Research InstitutionUniversity of Toyama

Principal Investigator

常山 幸一  University of Toyama, 大学院・医学薬学研究部, 准教授 (10293341)

Co-Investigator(Kenkyū-buntansha) 高野 康雄  富山大学, 大学院・医学薬学研究部, 教授 (60142022)
KeywordsNASH / 動物モデル / 酸化ストレス / 糖化反応 / 漢方薬 / AGE / RAGE / ガレクチン3
Research Abstract

非アルコール性脂肪性肝炎"non-alcoholic steatohepatitis (NASH)"は、糖尿病や肥満、高脂血症などの「生活習慣病」を背景として出現する進行性肝疾患であり、早急な社会的対応が望まれている。しかしながら、その病態はいまだ十分に解明されておらず、診断法の確立や適切な予防法・治療法の開発が急務である。本研究では、ヒト肝生検組織、及びNASHモデル動物を用いて、NASHの発症・進展メカニズムを多角的に解析することを目的としている。平成19年度は異なるメカニズムによって発症する新規NASHモデルを2つ報告し、以前に報告したNASHモデル(ガレクチン3欠損マウス、高コレステロール食負荷ウサギ)と併せて病態機序の解明や漢方薬等の効果について検討した。1.肥満、糖尿病、高血圧等を発症するモデル動物の肝病変を検討し、ヒトのNASHに極めて類似するモデル動物を新たに2つ報告した。(MSGマウス、SHR/NDmcr-cpラット)2.以前に報告したAGE受容体欠損モデルであるガレクチン3欠損マウスが、12カ月齢以降、重篤な線維化を背景に高率に肝細胞癌を発症することを報告した。3.高コレステロール食負荷ウサギの肝病変に、いくつかの漢方薬が高い予防効果を示した。なかでも桂枝茯苓丸はアディポネクチンを有意に増加させた。4.酸化ストレスが肝細胞、胆管上皮細胞に障害を与える機序について、種々のモデル動物を用い、分子病理学的、病理形態学的に検討した。

  • Research Products

    (16 results)

All 2008 2007

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (5 results)

  • [Journal Article] (MSG): a villain and promoter of liver inflammation and dysplasia2008

    • Author(s)
      Nakanishi Y
    • Journal Title

      J. Autoimmun 30

      Pages: 42-50

    • Peer Reviewed
  • [Journal Article] A possible rat model for non-alcoholic steatohepatitis: Histological findings in SHR/NDmcr-cp rats2008

    • Author(s)
      Kato S
    • Journal Title

      Hepatology research (In press)

    • Peer Reviewed
  • [Journal Article] Nonalcoholic steatohepatitis and hepatocellular carcinoma in Galectin-3 knockout Mice2008

    • Author(s)
      Nakanishi Y.
    • Journal Title

      Hepatology reserch (In press)

    • Peer Reviewed
  • [Journal Article] Evidence-based efficacy of Kampo formulas in a model of non alcoholic fatty liver2008

    • Author(s)
      Fujimoto M
    • Journal Title

      Exp Biol Med 233

      Pages: 328-37

    • Peer Reviewed
  • [Journal Article] Cytoplasmic fine granular expression of 8-hydroxydeoxyguanosine reflects early mitochondrial oxidative DNA damage in nonalcoholic fatty liver disease2008

    • Author(s)
      Nomoto K
    • Journal Title

      Appl Immunohistochem Mol Morphol 16

      Pages: 71-5

    • Peer Reviewed
  • [Journal Article] Biliary enithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells2008

    • Author(s)
      Shimoda S.
    • Journal Title

      Hepatology 47

      Pages: 958-65

    • Peer Reviewed
  • [Journal Article] Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis2008

    • Author(s)
      Oertelt-Prigione S
    • Journal Title

      Autoimmunity 30

      Pages: 42-50

    • Peer Reviewed
  • [Journal Article] Oxidative stress-induced apoptosis of bile duct cells in primary biliary cirrhosis2007

    • Author(s)
      Salunga TL
    • Journal Title

      J Autoimmun 29

      Pages: 78-86

    • Peer Reviewed
  • [Journal Article] Gene expression profiling in whole liver of bile duct ligated rats: VEGFA expression is up-regulated in hepatocytes adjacent to the portal tracts2007

    • Author(s)
      Tanaka A
    • Journal Title

      J Gastroenterol Hepatol 22

      Pages: 1993-2000

    • Peer Reviewed
  • [Journal Article] Induction of primary biliary cirrhosis in guinea pigs following chemicalx enobiotic immunization2007

    • Author(s)
      Leung PS
    • Journal Title

      J Immunol 179

      Pages: 2651-7

    • Peer Reviewed
  • [Journal Article] Knock down of gamma-glutamylcysteine synthetase in rat causes aceta minophen-induced hepatotoxicity2007

    • Author(s)
      Akai S.
    • Journal Title

      J Biol Chem 282

      Pages: 23996-4003

    • Peer Reviewed
  • [Presentation] Evidence-Based Efficacy of Kampo Formulas on Liver Pathology in a Rabbit Model of Non Alcoholic Fatty Liver Disease2007

    • Author(s)
      Fujimoto M
    • Organizer
      The 14th International Congress of Oriental Medi cine
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2007-12-10
  • [Presentation] The Traditional Japanese Kampo Formula keishibukuryogan Ameliorates Steatosis, Reduces Oxidative Stress and Inflammation, and Ultimately Prevents Liver Fibrosis in a Rabbit Model of Non Alcoholic Steatohepatitis2007

    • Author(s)
      Fujimoto M
    • Organizer
      The 58th Annual Meeting of The American Association for The Study of Liver Diseases
    • Place of Presentation
      Boston, USA
    • Year and Date
      2007-11-07
  • [Presentation] Impairment of the indoleamine 2,3-Dioxygenase pathway in primary biliary cirrhosis2007

    • Author(s)
      Oertelt-Prigione S
    • Organizer
      The 58th Annual Meeting of The American Association for The Study of Liver Diseases
    • Place of Presentation
      Boston, USA
    • Year and Date
      2007-11-05
  • [Presentation] Induction of primary biliary cirrhosis in guinea pigs using chemical xenobiotic immunization: implications for tolerance and the etiology of hum an PBC2007

    • Author(s)
      Leung PS
    • Organizer
      The 58th Annual Meeting of The American Association for The Study of Liver Diseases
    • Place of Presentation
      Boston, USA
    • Year and Date
      2007-11-05
  • [Presentation] メタボリツクシンドロームモデル動物に出現する非アルコール性脂肪性肝障害(NAFLD)の病理学的特徴2007

    • Author(s)
      常山 幸一
    • Organizer
      第3回TSOD(肥満・糖尿病)マウス研究会情報交換会
    • Place of Presentation
      東京
    • Year and Date
      2007-08-10

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Published: 2010-02-04   Modified: 2016-04-21  

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