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ATP感受性Kチャネル開口薬による肝再生の促進

Research Project

Project/Area Number 19659345
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionOsaka City University

Principal Investigator

裴 正寛  Osaka City University, 大学院・医学研究科, 登録医 (30423883)

Co-Investigator(Kenkyū-buntansha) 竹村 茂一  大阪市立大学, 大学院・医学研究科, 講師 (00322363)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2008: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords肝再生 / Kチャネル / 再生不全 / 糖尿病
Research Abstract

糖尿病症例では、肝切除後の肝再生の遅延ならびに肝機能障害の遷延、ひいては肝不全の出現頻度が高いがその機序は十分に解明されておらず、その対策も無い。本研究では種々の細胞の成長、増殖を促進するATP感受性Kチャネル開口薬の肝再生に及ぼす効果を検討し肝切除後肝再生を促進し、さらには糖尿病合併例における肝切除の安全性の向上を目指す。
我々は平成19年度にMinoxidil、CromakalimなどのKチャネル開口薬は肝癌細胞株、HGF刺激下初代培養肝細胞、肝部分切除の前処置による肝再生を10〜20倍に亢進させKチャネル遮断薬であるGlibencramideにより濃度依存性に抑制されることを報告した。平成20年度は、自然発症2型糖尿病モデルラットであるOtsuka Long Evans Tokushima Otsukaラット(OLETF)を用い、対照ラットであるLETOと比較検討した。昨年のF344ラットの肝部分切除後の肝再生に対する促進と同様、OLETFおよびLETOラットに対しても肝部分切除後の肝再生を促進することが判明した。しかし、糖尿病ラット(OLETF)における肝切除術後の肝機能障害の遷延ならびに肝不全の出現は抑制できなかった。詳細な検討の結果、糖尿病ラットでは肝切除前より肝細胞酸化ストレスが増加しており、ミトコンドリアのNa勾配を維持し、ラジカル消去作用を有するある種のたんぱく質が肝切除後肝再生という更に酸化ストレスが増加する状況下においても誘導されること無く細胞障害が遷延することを見出した。
本研究により、Kチャネル開口薬による肝再生促進の可能性のみならず、糖尿病患者における肝切除後肝障害の遷延のメカニズムを解明することができた。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (24 results)

All 2009 2008 2007

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (13 results)

  • [Journal Article] S-allylcysteine is effective as a chemopreventive agents for porcine serum-induced hepatic fibrosis in rats.2009

    • Author(s)
      Shinkawa H, Takemura S, Minamiyama Y, et al.
    • Journal Title

      Osaka City Medical Journal (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma.2009

    • Author(s)
      Ichikawa T, Uenishi H, Takemura S, et al.
    • Journal Title

      Journal of Hepatobiliary-Pancreatic Surgery 16

      Pages: 42-48

    • NAID

      10025137704

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous measurement of F(2)-isoprostane, hydroxyocta-decadienoic acid, hydroxyeicosatetraenoic acid, and hydroxy-cholesterols from physiological samples.2008

    • Author(s)
      Yoshida Y, Kodai S, Takemura S, et al.
    • Journal Title

      Analytical Biochemistry 379

      Pages: 105-115

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of CYP3A aggravates endotoxin-induced liver injury in hypophysectomised female rats.2008

    • Author(s)
      Takemura S, Minamiyama Y, Toyokuni S, et al.
    • Journal Title

      Hepatology Research 38

      Pages: 70-78

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Response to interferon therapy affects risk factors for post-operative recurrence of hepatitis C virus-related hepatocellular carcinoma.2008

    • Author(s)
      Uenishi, Nishiguchi S, Tanaka S, et al.
    • Journal Title

      Journal of surgical Oncology 98

      Pages: 358-362

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary resection for non-small cell lung cancer in patients with hepatocellular carcinoma.2008

    • Author(s)
      Iwata T, Nishiyama N, Nagano K, et al.
    • Journal Title

      World Journal of Surgery 32

      Pages: 2204-2212

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Convenience of a tape-guiding technique in different types of hepatectomy.2008

    • Author(s)
      Tanaka H, Takemura S, Oba K, et al.
    • Journal Title

      Hepatogastroenterology 55

      Pages: 160-163

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocellular carcinoma (HCC) recurring 10 years after clearance of Hepatitis B surface antigen and 20 years after of Hepatitis B virus-related HCC.2008

    • Author(s)
      Shinkawa H, Nakai T, Tamori A, et al.
    • Journal Title

      International Journal of Clinical Oncology 13

      Pages: 562-566

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of CYP3A aggravates endotoxin-induced liver injury in hypophysectomized female rats.2008

    • Author(s)
      Takemura S, et. al.
    • Journal Title

      Hepatology Research 38

      Pages: 70-78

    • NAID

      10020117058

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Supplementation of-tocopherol inproves cardiovascular risk factors via theinsulin signalling pathway and reduction of mitochondrial reactive oxygenspecies in type II diabetic rats.2008

    • Author(s)
      Minamiyama Y, Takemura S, et al.
    • Journal Title

      Free Radical Research 42

      Pages: 261-271

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats.2007

    • Author(s)
      Minamiyama Y, Takemura S, et. al.
    • Journal Title

      The Journal of Pharmacology and Experimental Therapeutics 320

      Pages: 535-543

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] ニコランジルが他の硝酸製剤と異なる理由-チトクロームP450とニトロ耐性の観点から-2008

    • Author(s)
      南山幸子, 他
    • Organizer
      第21回ニコランジル研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Sアリルシステインの肝線維化抑制効果に関するTGF-βシグナルの関与2008

    • Author(s)
      高台真太郎, 他
    • Organizer
      第12回日本肝臓学会大会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] 遺伝的2型糖尿病ラットにおける鉄制限治療の効果2008

    • Author(s)
      南山幸子, 他
    • Organizer
      第32回日本鉄バイオサイエンス学会
    • Place of Presentation
      青森
    • Year and Date
      2008-09-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] 肥満を伴う2型糖尿病OLETFラットにおけるαトコフェロールとγトコフェロールの治療効果の比較2008

    • Author(s)
      南山幸子, 他
    • Organizer
      第8回日本抗加齢医学会総会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] ブタ血清誘発肝線維化におけるSアリルシステインの抑制効果2008

    • Author(s)
      新川寛二, 他
    • Organizer
      第108回日本外科学会定期学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 肝星細胞活性化に関するSアリルシステインの抑制効果とその機序2008

    • Author(s)
      高台真太郎, 他
    • Organizer
      第94回日本消化器病学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2008-05-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] S-allyl cysteine attenuates the progression of pig serum-induced liver fibrosis in rats.2008

    • Author(s)
      Kodai S, Takemura S, Minamiyama Y, et al.
    • Organizer
      43^<rd> annual meeting of the European association for the study of the liver
    • Place of Presentation
      Milan(Italy)
    • Year and Date
      2008-04-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] The effect of S-allyl cysteine on CCL4-induced liver fibrosis and hepatic stellate cells activation.2008

    • Author(s)
      Shinkawa H, Takemura S, Minamiyama Y, et al.
    • Organizer
      43^<rd> annual meeting of the European association for the study of the liver
    • Place of Presentation
      Milan(Italy)
    • Year and Date
      2008-04-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] Attenuation of reactive over-expression of uncoupling 2 after partial hepatectomy aggravates oxidative damage in Otsuka Long Evans Tokushima Fatty rats.2008

    • Author(s)
      Takemura S, et. al.
    • Organizer
      Biomarkers of Oxidative Stress in Health and Diseases2008
    • Place of Presentation
      Osaka,Japan
    • Year and Date
      2008-01-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Alpha-tocopherol,but not gamma-tocopherol,improves diabetic complica-tions in type II diabetic rats2008

    • Author(s)
      Minamiyama Y, Takemura S, et. al.
    • Organizer
      Biomarkers of Oxidative Stress in Health and Diseases2008
    • Place of Presentation
      Osaka,Japan
    • Year and Date
      2008-01-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Alpha-tocopherol improves diabetic complications via the reduction of mitochondrial reactive oxygen species in type II diabetic rats.2007

    • Author(s)
      Minamiyama Y, Takemura S, et. al.
    • Organizer
      4th Joint Meeting of the Society For Free Radical Research Australasia and Japan
    • Place of Presentation
      Kyoto,Japan
    • Year and Date
      2007-12-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] 糖尿病ラットにおける肝切除後のミトコンドリア由来活性酸素産生と肝障害2007

    • Author(s)
      竹村 茂一, 他
    • Organizer
      第11回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2007-10-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] 糖尿病態下の肝切除後再生時の活性酸素とUCP2の誘導2007

    • Author(s)
      竹村 茂一, 他
    • Organizer
      第107回日本外科学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-12
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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