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Mechanistic Investigation of Regulation of Hepatic Ischemia and Reperfusion Injury and Promotion of Hepatic Regeneration

Research Project

Project/Area Number 13671282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

YOSHIDOME Hiroyuki  Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (10312935)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Hiroaki  Chiba University, University Hospital, Lecturer, 医学部附属病院, 講師 (80272318)
MIYAZAKI Masaru  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (70166156)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsischemia / reperfusion / chemokine / transcriptional factor / neutrophil / preconditioning / 肝阻血再灌流障害 / NFκB / NF_(k)B
Research Abstract

BACKGROUND. Interruption of hepatic inflow during hepatectomy (Pringle's maneuver) and vascular reconstruction of hepatic transplantation causes hepatic ischemia. An acute inflammation associated with this unfavorable event induces significant organ damage/dysfunction. Regulation of hepatic ischemia/reperfusion injury (I/R) is an important clinical consideration.
METHODS. Using a murine model of partial hepatic ischemia and reperfusion, we investigated endogenous regulation of IL-18 in this inflammatory injury.
RESULTS. Hepatic ischemia for 90 minutes and reperfusion for up to 8 hours upregulated IL-18 expression. Hepatic I/R activates transcriptional factor, NF-κB and AP-1. In addition, hepatic I/R caused significant increases in liver neutrophil recruitment, hepatocellular injury, and liver edema, as defined by liver myeloperoxidase content, serum ALT, and liver wet to dry weight ratios, respectively. In mice treated with neutralizing antibody to IL-18, I/R -induced increases in CXC chemokine expression and activation of transcriptional factor were greatly diminished. Furthermore, under blockade of IL-18, anti-inflammatory cytokines such as IL-4 and IL-10 were greatly upregulated. These conditions also caused significant reductions in liver neutrophil sequestration and liver injury.
CONCLUSIONS. The data suggest that IL-18 is required for facilitating neutrophil-dependent hepatic ischemia and reperfusion injury through suppressing anti-inflammatory cytokine expression.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Takeuchi D, Yoshidome H, Miyazaki M, et al.: "Role of ELR negative CXC and CC chemokines in hepatic ischemia/reperfusion injury"Proceedings of the 37^<th> Congress of the European Society for Surgical Research. 37. 293-297 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshidome H, Shimizu H, Miyazaki M, et al.: "Role of ELR negative CXC and CC chemokines in hepatic ischemia/reperfusion injury"Proceedings of the 37^<th> Congress of the European Society for Surgical Research. 37. 147-152 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kataoka M, Shimizu H, Yoshidome H, Miyazaki M, et al.: "Effect of cold-ischemia time on C-X-C chemokine expression and neutrophil accumulation in the graft liver after orthotopic liver transplantation in rats"Transplantation. 73. 1730-1735 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura F, Shimizu H, Yoshidome H, Miyazaki M, et al.: "Long-term results of initial and repeated partial splenic embolization for the treatment of chronic idiopathic thrombocytopenic purpura"AJR Am J Roentgenol. 179. 1323-1326 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshidome H, Shimizu H, Miyazaki M, et al.: "Surgical Treatment for Extrahepatic Recurrence after Hepatectomy for Colorectal Metastases"Hepatogastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitayama D, Yoshidome H, Shimizu H, Miyazaki M, et al.: "Aggressive Surgical Resection for Hepatocellular Carcinoma with Tumor Thrombus Extending to Inferior Vena Cava and Synchronous Pulmonary Metastasis"Hepatogastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi D, Yoshidome H, Morita Y, Ito H, Kimura F, Shimizu H, Ohtsuka M, Miyazaki M.: "Role of ELR negative CXC and CC chemokine in hepatic ischemia/reperfusion injury"Proceedings of the 37th Congress of the European Society for Surgical Research, Mihaly Boros ed.. 293-297 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi D, Yoshidome H, Miyazaki M, et al.: "Role of ELR negative CXC and CC chemokines in hepatic ischemia/reperfusion injury"Proceedings of the 37^<th> Congress of the European Society for Surgical Research. 37. 293-297 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshidome H, Shimizu H, Miyazaki M, et al.: "Surgical treatment for recurrence of the remnant liver and lung after hepatic resection for colorectal metastases"Proceedings of the 37^<th> Congress of the European Society for Surgical Research. 37. 147-152 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kataoka M, Shimizu H, Yoshidome H, Miyazaki M, et al.: "Effect of cold-ischemia time on C-X-C chemokine expression and neutrophil accumulation in the graft liver after orthotopic liver transplantation in rats"Transplantation. 73. 1730-1735 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimura F, Shimizu H, Yoshidome H, Miyazaki M, et al.: "Long-term results of initial and repeated partial splenic embolization for the treatment of chronic idiopathic thrombocytopenic purpura"AJR Am J Roentgenol. 179. 1323-1326 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshidome H, Shimizu H, Miyazaki M, et al.: "Surgical Treatment for Extrahepatic Recurrence after Hepatectomy for Colorectal Metastases"Hepatogastroenterology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitayama D, Yoshidome H, Shimizu H, Miyazaki M, et al.: "Aggressive Surgical Resection for Hepatocellular Carcinoma with Tumor Thrombus Extending to Inferior Vena Cava and Synchronous Pulmonary Metastasis"Hepatogastroenterology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimizu H, et al.: "Vascular endothelial growth factor secreted by replicating hepatocytes induces sinusoidal cell proliferation during regeneration after partial hepatectomy in rats"J Hepatol. 34. 683-689 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeuchi D, et al.: "Role of ELR negative CXC and CC chemokines in hepatic ischemia/reperfusion injury"Eur Surg Res. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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