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The developmental mechanism of liver failure after hepatectomy in aged and the effect of growth factor administration

Research Project

Project/Area Number 10671228
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKINKI UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

NOMURA Hideaki  Kinki University School of Medicine Lecture, 医学部, 講師 (20248040)

Co-Investigator(Kenkyū-buntansha) OHYANAGI Harumasa  Kinki University School of Medicine Professor, 医学部, 教授 (00030958)
HAJI Seiji  Kinki University School of Medicine Lecture, 医学部, 講師 (80288935)
KURODA Daisuke  Kinki University School of Medicine Lecture, 医学部, 講師 (30248041)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsaged / hepatectomypostoperative / liver failure / apoptosis / oxidative stress / IGF-1 / Kupffer cells
Research Abstract

【Aim】
It is admitted that elderly patients are vulnerable to various organ failures after surgical operations. But it is not well elucidated the mechanism of organ failures and surgical stress. This study was designed to be clarified the onset of hepatocellular dysfnction and surgical stress in aged animals from the view points of cytokine balance, oxidative stress and hepatocellular apoptosis induction.
【Material and method】
The old (60〜80 weeks of age) and young (6〜8 weeks of age) Wistar male rats were divided into O-group and Y-group, respectively. In vivo study, the survival rate, serum TNF-α, IL-10, serum GPT level, lipid peroxide in liver tissue, apoptosis induction (TUNEL), and ICEp10 expression (immunohistochemical staining) were measured in 70 % hepatectomized rats with 0.5 mg/kg of LPS at 48hours after the operation. In vivo study, hepatocytes and Kupffer cells were isolated from and co-cultured in double chamber, which is separated with multipore membrane. The hepatocytes were … More obtained at 4, 24 hours after the stimulation of Kupffer cells with 10μg/ml of LPS.Per oxide in hepatocytes and Apoptotic cells were analysed with flow cytometry fluorecent staining with DCFH-DA method and FITC-TUNEL method, respectively.
【Results】
In vivo study, the survival rate of O group (10%) was significantly reduced campared with that of Y group (100%). The levels of serum TNF-αpeaked at one hour after LPS stimulation in both group without any difference, but in O group it was prolonged tobe higher level up to 4 hours. The level of IL-10 showed remarkedly increased and prolonged in O group, while that in Y group remained to be low. GTP and liver tissue LPO level were increased significantly in O group, and The apoptosis cells and ICE p10 expression could be admitted diffusely dispersed in O group. Invitro study, there was no difference of LPO in liver tissue at 4 hours between Y and O group, but was significant differences at 24 hours between increased level of O group and decreased in Y group at 24 hours. Apoptotic cells could be recognized higher in O group.
【Conclusions】
In O group, excessive and prolonged physiological responses against the surgical stress could be seen compared with in Y group, resulting with the fluctuation of inflammatory cytokine (TNF-α) and antiinflammatory cytokine (IL-10). Moreover, the increased oxidative stress and hepatocellular apoptosis in vivo and vitro study concluded that the prolonged inflammatory responsesand induction of hepatocellular apoptosis caused with amplified oxidative stress elicit liver failure in aged animals. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 野村秀明,安田篤,安田健司,土師誠二,大柳治正: "腸管の生体防御機構"消化器外科. 24・1. 87-95 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 安田健司,土師誠二,野村秀明,安田篤,大柳治正: "ラット重症急性膵炎における小腸の形態的・機能的変化とIGF-1/IGFB0-3投与効果に関する実験的検討"外科と代謝・栄養. 34・6. 283-292 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 大柳治正,土師誠二: "外科感染症のリスクファクター-最近の知見-"Surgery Frontier. 7・4. 359-365 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 土師誠二,野村秀明,大柳治正: "侵襲時の神経・内分泌反応に関する新知見"Surgery Frontier. 7・3. 246-253 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 土師誠二,野村秀明,大柳治正: "SIRSと神経内分泌"現代医療. 32・別冊. 2131-2137 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 野村秀明,土師誠二,大柳治正: "多臓器障害とサイトカイン"外科治療. 81・5. 597-604 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] NOMURA Hideaki, YASUDA tsushi, YASUDA Keinji, HAJI Seiji, OHYANAGI Harumasa: "Physiological protective mechanism of the gut."Gastroenterological Surgery. vol.24 No.1. 87-95 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] YAUDA Kenji, HAJI Seiji, NOMURA Hideaki, YASUDA Atsushi, OHYANAGI Harumasa: "The Morphological and Functional Changes of the Small Intesine and the Benefical Effect of IGF-1/IGFBP-3 Complex in Severe Acute Pancreatitis in Rats."The Japanese Journal of SURGICAL METABOLISM and NUTRITION. vol.34 No.6. 283-292 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] OHYANAGI Harumasa, HAJI Seiji: "Risk factor of post operative infection."Surgery Frontier. vol.7 No.4. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] HAJI Seiji, NOMURA Hideaki, OHYANAGI Harumasa: "The neuroendocrine responses under surgical stress."Surgery Frontier. vol.7 No.3. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] HAJI Seiji, NOMURA Hideaki, OHYANAGI Harumasa: "Relationship between systemic inflammatory response syndrome and neuroendocrine system"GENDAIIRYOU. vol.32 suppl.. 2131-2137 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] NOMURA Hideaki, HAJI Seiji, OHYANAGI Harumasa: "Multiple organs dysfunction syndrome and cytokines."SURGICAL THERAPY. vol.81 No.5. 597-604 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 野村秀明,安田篤,安田健司,土師誠二,大柳治正: "腸管の生体防御機構"消化器外科. 24・1. 87-95 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 安田健司,土師誠二,野村秀明,安田篤,大柳治正: "ラット重症急性膵炎における小腸の形態的・機能的変化とIGF-1/IGFB0-3投与効果に関する実験的検討"外科と代謝・栄養. 34・6. 283-292 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大柳治正,土師誠二: "外科感染症のリスクファクター-最近の知見-"Surgery Frontier. 7・4. 359-365 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 土師誠二,野村秀明,大柳治正: "侵襲時の神経・内分泌反応に関する新知見"Surgery Frontier. 7・3. 246-253 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 土師誠二,野村秀明,大柳治正: "SIRSと神経内分泌"現代医療. 32・別冊. 2131-2137 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 野村秀明,土師誠二,大柳治正: "多臓器障害とサイトカイン"外科治療. 81・5. 597-604 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 土師誠二、野村秀明、大柳治正: "老人外科における侵襲と対策"外科治療. 81・10. 221-222 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 野村秀明、土師誠二、大柳治正: "高齢者の神経・内分泌反応"Surgery Frontier. 5・4. 359-366 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 野村秀明、土師誠二、大柳治正: "多臓器障害とサイトカイン"外科治療. 81・11. 597-604 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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