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2003 Fiscal Year Final Research Report Summary

Study of the mechanism of liver ischemia-repeifusion injuiy based on modulation of NF-kB activation by gene transfer technique

Research Project

Project/Area Number 13671235
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionHiroshima University

Principal Investigator

MARUBAYASHI Seiji  Hiroshima University, Medical and Dental Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (80144814)

Co-Investigator(Kenkyū-buntansha) TASHIRO Hirotaka  Hiroshima University, Medical and Dental Hospital, Research Associate, 医学部・歯学部附属病院, 助手
YAHATA Hiroshi  Hiroshima University, Medical and Dental Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (10191181)
Project Period (FY) 2001 – 2003
KeywordsNF-kB decoy / endotoxin-induced liver injury / liver ischemia-reperfusion / NF-kB / cytokine / TNF-alpha
Research Abstract

The NF-kB is a ubiquitous transcriptional factor involved in the up-regulation of many inflammatory response. We recently demonstrated that NF-kB activity increased during the hepatic ischemia-reperfusion and endotoxin induced shock liver. The present study was undertaken to determine whether NF-kB decoy could suppress proinflammatory gene up-regulation through inhibition of NF-kB activation in endotoxin shock or acute liver rejection model and increase the survival rate of animals. Treatment with NF-kB decoy injected in the portal vein significantly increased survival rates 24 and 48 hours after lipopolysaccharide injection and suppressed the increase of plasma TNF-alpha activity. NF-kB decoy treatment showed inhibitory effect on hydrogen peroxide induced NF-kB activation in Jurkat cells. in the acute liver rejection model in the rat liver transplantation (donor ; DA rats, recipient ; Lewis rats), treatment with NF-kB decoy in the preservation fluid significantly suppressed expression of inflammatory cytokine mRNA and increased the survival rate of the recipient rats. These results suggest that NF-kB decoy can suppress proinflammatory cytokine up-regulation through inhibition of NF-kB activation and it is a promising new drug for the treatment of endotoxin shock and acute liver rejection.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 丸林 誠二: "エンドトキシン肝障害に及ぼすラザロイドの投与効果"G.I.Research. 9(4). 79-80 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Marubayashi: "Effect of lazaroids on NF-κB activation of Kupffer cells in liver preservation"Transplant Proc. 34(7). 2662-2663 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Mizunuma: "Beneficial Effects of a Rho-Associated Coiled-Coli Forming Protein Serine/Threonine kinase Inhibitor, Y-27632,on Survival of Recipients in Rat Liver Transplantation Following Warm Ischemia"Transplant Proc. 34. 2643-2644 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Okada: "Novel Method Using Near-Infrared Spectroscopy to Assess Intrahepatic Anastomosis Between Hepatic Veins of Right Lobe Graft in Living-Donor Liver Transplantion."Transplant Proc. 34. 2781 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 丸林 誠二: "エンドトキシン肝障害に対するラザロイドおよびNF-κB decoyの効果"G.I.Research. 10(4). 324 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 丸林 誠二: "特集、肝胆膵疾患とNF-kB:最近の話題。エンドトキシン肝障害とNF-κB抑制。"肝胆膵. 46(1). 59-65 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 丸林 誠二: "外科侵襲と酸化ストレス"医薬の門. 43(5). 579-585 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北山 輝彦: "エンドトキシン肝障害機構と各種薬剤による投与効果"G.I.Research. 11(4). 354-355 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Marubayashi: "Effect of Monoclonal Antibodies to Adhesion Molecules, Nitric Oxide Synthase Inhibitors, Methylprednisolone and Lazaroid on Endotoxin-Induced Liver Cell Injury. T Yoshikawa (ed):Oxidative stress and Digestive diseases"Karger, Basel. 119-135 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 丸林 誠二: "腹部重症感染症に対するエンドトキシン吸着療法(PMX-DHP)"金原出版株式会社(印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Marubayashi: "Effect of lazaroid on endotoxin-induced liver cell Injury"G.I. Research. 9(4). 79-80 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Marubayashi: "Effect of lazaroids on NF-κB activation of Kupffer cells in liver preservation"Transplant Proc. 34(7). 2662-2663 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Mizunuma: "Beneficial Effects of a Rho-Associated Coiled-Coli Forming Protein Serine/Threonine kinase Inhibitor : Y-27632,on Survival of Recipients in Rat Liver Transplantation Following Warm Ischemia"Transplant Proc. 34. 2643-2644 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Obdan: "Novel Method Using Near-Infrared Spectroscopy to Assess Intrahepatic Anastomosis Between Hepatic Veins of Right Lobe Graft in Living-Donor Liver Transplantion"Transplant Proc. 34. 2781 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Marubayashi: "Effect of lazaroid and Nf-kB decoy on endotoxin Induced liver damage"G.I.Research. 10(4). 324 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Marubayashi: "Review : hepato-bihary-pancreatic diseases and Nf-kB ; recent topics. Endotoxinin-incluced liver Damage and inhibition of NP-kB activation"KanTanSui. 46(1). 59-65 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Marubayashi: "Surgical attack and oxidative stress"Iyakunomon. 43(5). 579-585 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Marubayashi: "Effect of Monoclonal Antibodies to Adhesion Molecules, Nitric Oxide Synthase Inhibitors, Methyiprednisolone and Lazaroid on Endotoxin-Induced Liver Cell Injury (T Yoshikawa (ed) : Digestive)"Oxidative stress and Digestive diseases Karger, Basel (T.Yoshikawa (ed)). 119-135 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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