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Mechanism of vulnerability to endotoxin of regenerating liver and its treatment

Research Project

Project/Area Number 10671170
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

NAKAMURA Satoshi  Hamamatsu University School of Medicine, Second Department of Surgery, Professor, 医学部, 教授 (00090027)

Co-Investigator(Kenkyū-buntansha) ODA Toshiaki  Hamamatsu University School of Medicine, First Department of Biochemistry, Associate Professor, 医学部, 助教授 (90126805)
SUZUKI Shohachi  Hamamatsu University School of Medicine, Second Department of Surgery, Assistant Professor, 医学部・附属病院, 講師 (20196827)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsHepatic resection / Endotoxin / Platelet-activating factor / PAF-receptor / TNF-a / NF-kB / hepatic regeneration / PAF / CINC / NF-κB / LPS / TNF2 / TNFα
Research Abstract

Background. Platelet-activating factor (PAF) has been shown to be an important mediator in the pathogenesis of lipopolysaccharide (LPS)-induced liver ijury in regenerating rat livers. Both LPS and PPAF activate nuclear factor-kappa B (NF-kB), a key transcription factor for tumor necrosis factor-a (TNF-a) and cytokine-induced neutrophil attractant (CINC). The aim of this study is to investigate how PAF participates in the LPS-induced and NF-kB-mediated regulation of TNF-a and CINCin regenerating rat livers.
Methods. LPS (1.5 mg/kg) was intravenously administered into 70 % hepatectomized rats and sham-operated rats 46 hours postoperatively.
Results. LPS administration caused a high mortality rate, scattered necrosis in the liver with infiltration of CINC-positive neutrophils, and a continuous CINC messenger RNA up-regulation and activation of NF-kB in the liver only in hepatectomized rats. These phenomena were all effectively prevented by pretreatment and posttreatment with a PAF receptor antagonist, TCV-309. Heptectomized rats showed NF-kB staining in hepatocytes, Kupffer cells, and neutrophils around necrosis 4 hours after the LPS injection, representing the activation of this factor in these cells.
Conclusions. Based on these results, we propose that PAD contributes to continuous CINC up-regulation and NF-kB activation via accumulation and activation of neutrophils, and thereby is involved in LPS-induced liver injury in regenerating rat liver.

Report

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

Research Products

(9 results)

All Other

All Publications (9 results)

  • [Publications] Suzuki S. et al.: "The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic inchemia and reperfusion"Transplantation. 69. 2267-2273 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takanori Sakaguchi, Satoshi Nakamura, et al.: "Participation of platelet-activating factor in the lipopolysaccharide-induced injury in partially hepatectomized rats."Hepatology. 30. 959-967 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takanori Sakaguchi, Satoshi Nakamura, et al.: "Acute portal hypertension increases ileal vulnerability to platelet-activating factor in rats."J Surg Res. 86. 116-122 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shohachi Suzuki, Satoshi Nakamura, et al.: "The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion."Transplantation. 69. 2267-2273 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakaguchi T, et al.: "Participation of platelet-activating factor in the lipopolysaccharide-induced injury in partially hepatectomized rats."Hepatology. 30. 959-967 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakaguchi T, et al.: "Acute portal hypertension increases ideal vulnerability to platelet-activating factor in rats."J.Surg.Res.. 86. 116-122 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki S, et al.: "The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion"Transplantation. 69. 2267-2273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 坂口孝宣: "Participation of platelet-Activating Factor in the Lipoplysacharide-Induced liver injury in partially hepatectomized rats"Hepatology. 30. 959-967 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 坂口孝宣: "Acute portal hypertension increases ileal Vulnerability to platelet-activating factor in rats"Journal of Surgical Research. 86. 116-122 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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