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Contribution of heme oxygenase-1 to the outcome after partial hepatectomy for ischemically damaged steatotic rat liver

Research Project

Project/Area Number 15591395
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SUZUKI Shohachi  Hamamatsu University School of Medicine, Second Department of Surgery, Associate Professor, 医学部, 助教授 (20196827)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Satoshi  Hamamatsu University School of Medicine, University Hospital, Director, 医学部, 理事 (00090027)
MITSUOKA Hiroshi  Hamamatsu University School of Medicine, Instructor, 医学部附属病院, 助手 (10324360)
坂口 孝宣  浜松医科大学, 医学部, 助手 (70313955)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsSteatotic liver / Hepatic ischemia / Reperfusion injury / Hepatectomy / Liver regeneration / Heme oxygenase 1
Research Abstract

Background : The pathophysiologic mechanism for the increased vulnerability of steatotic livers to normothermic ischemia and reperfusion injury during partial hepatectomy is yet insufficiently clarified. Heme oxygenase-1 is an antioxidative enzyme which catabolizes heme into biliverdin, carbon monoxide, and iron. This study was conducted to determine the contribution of HO-1 to the outcome after partial hepatectomy for steatotic liver with ischemic insult.
Methods : Male Wistar rats, 4 weeks of age, undergoing splenic transposion to produce spontaneous portosystemic shunt were fed a fat-enriched diet for 4 or 12 weeks to produce the fatty liver. Animals from each group were subjected to 60 minutes of total hepatic ischemia. A two-thirds hepatectomy was performed just before reperfusion. In addition of 7-day survival rates, the assessment of plasma aspartate transaminase (AST) levels, hepatic HO-1 expression, and liver histology was performed 6 hours after reperfusion.
Results : The exten … More t of hepatic steatosis was mild to moderate in animals fed with a fat-enriched diet for 4 weeks and severe in animals fed with a fat-enriched diet for 12 weeks. Six hours after partial hepatectomy, focal necrosis with sinusoidal congestion and neutrophil accumulation was observed in the livers of the control group. Extensive necrosis was seen in severe steatotic liver at the corresponding time. Significantly less histological damage was seen in mild to moderate steatotic liver, when compared with severe steatotic liver. Plasma AST levels in animals fed with a fat-enriched diet for 4 or 12 weeks reached 5517±685 IU/l and 8305±2684 IU/l, respectively, while those in the control group were 3462±1039 IU/l(P<0.01). HO-1 proteins were hardly detectable before induction of hepatic ischemia in the normal liver as well as in the mild and severe steatotic liver. HO-1 protein expression in the severe steatotic liver 6 hours after I/R injury was significantly weaker than those in the normal and the mild steatotic livers. While 7-day survival rates of animals fed with normal chow and a fat-enriched diet for 4 weeks were 50% and 42%, respectively, that of animals fed with a fat-enriched diet for 12 weeks was 25%.
Conclusions : The deficit of HO-1 expression may be a causal factor on poor functional and structural recovery after partial hepatectomy for severe steatotic liver with ischemic insult. The induction of HO-1 system may serve as a novel therapeutic strategy in liver surgery for steatotic liver. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

Research Products

(3 results)

All 2005 Other

All Journal Article (3 results)

  • [Journal Article] Sexual dimorphism in endotoxin susceptibility after partial hepatectomy in rats.2005

    • Author(s)
      Inaba K
    • Journal Title

      J Hepatol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sexual dimorphism in endotoxin susceptibility after partial hepatectomy in rats.

    • Author(s)
      Inaba K, Suzuki S, Ihara H, Sakaguchi T, Baba S, Urano T, Konno H, Nakamura S.
    • Journal Title

      J Hepatol (accepted for publication)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sexual dimorphism in endotoxin susceptibility after partial hepatectomy in rats.

    • Author(s)
      Inaba K
    • Journal Title

      J Hepatol (in press)

    • Related Report
      2004 Annual Research Report

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Published: 2003-03-31   Modified: 2016-04-21  

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