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Prevention of hepatic ischemia-reperfusion injury by gene transfer of IкB antisense and its application to liver transplantation

Research Project

Project/Area Number 13671342
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKeio University

Principal Investigator

SHIMAZU Motohide  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (70124948)

Co-Investigator(Kenkyū-buntansha) SHINODA Masahiro  Keio University, School of Medicine, Assistant, 医学部, 助手 (50286499)
TAKAYANAGI Atsushi  Keio University, School of Medicine, Assistant, 医学部, 助手 (80245464)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsIкB / NFкB / antisence / genetransfer / ischemia-reperfusion injury / liver transplantation / IkB / NFkB / 肝虚血再灌流傷害
Research Abstract

NFкB is a transcriptional factor which plays a major role in production of inflammatory cytokines and regulation of apoptosis. However, it is still unclear whether up-regulation of NFкB has a cytoprotective effect or not in hepatic ischemia-reperfusion injury. We already constructed a recombinant adenovirus vector expressing a truncated form of the inhibition protein IкB (Adex IкB), and demonstrated that transfer of Adex IкB inhibited NFкB activation and aggravated hepatic ischemia-reperfusion injury in rats. In the present study, we tried to construct Adex IкB antisense suppressing IкB production and investigated the effect of IкB antisense gene transfer to NFкB activation and ischemia-reperfusion injury. In vitro, amount of IкB was not decreased in cultured cells infected Adex IкB antisense, although IкB antisense cDNA was detected by RT-PCR. In hepatic ischemia-reperfusion model in rats, administration of Adex IкB antisense did not attenuate hepatic injury compared to the control group

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Morisue A, Wakabayashi G, et al.: "The role of Nitric Oxide after a short period of liver ischemia-reperfusion"J Surg Res. 109. 101-109 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinoda M, Shimazu M, et al.: "Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning"J Gastroenterol Hepatol. 17. 1211-1219 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada H, Wakabayashi G, et al.: "Transfer of Interleukin-1 receptor antagonist gene into rat liver abrogates hepatic ischemia-reperfusion injury"Transplantation. 74. 1434-1441 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinoda M, Shimazu M, et al.: "c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model"Wound Repair Regen. 10. 314-319 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto S, Shimazu M, et al.: "The Role of Tumor Necrosis Factor-α and Interleukin-1β in Ischemia-Reperfusin Injury of the Rat Small Intestine"J Surg Res. 99. 134-141 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato Y, Shimazu M, et al.: "Significance of Portal Venous Flow in Graft Regeneration After Living Liver Transplantation"Transplant Proc. 33. 1484-1485 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimazu M: "Trends in Gastroenterology and Hepatology"Ed. By Asakura H, Aoyagi Y and Nakazawa S, Springer Verlag. 370 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morisue,A, Wakabayashi,G, Shimazu,M, Mukai,M, Matsumoto,K, Kawachi,S, Yoshida,M, Yamamoto,S, Kitajima,M: "The role of Nitric Oxide after a short period of liver ischemia-reperfusion"J Surg Res. 109. 101-109 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinoda,M, Shimazu,M, Wakabayashi,G, Tanabe,M, Hoshino,K, Kitajima,M: "Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning"J Gastroenterol Hepatol. 17. 1211-1219 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada,H, Wakabayashi,G, Takayanagi,A, Shimazu,M, Matsumoto,K, Obara,H, Shimizu,N, Kitajima,M: "Transfer of the Interleukin-1 receptor antagonist gene into rat liver abrogates hepatic ischemia-reperfusion injury"Transplantation. 74. 1434-1441 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinoda,M, Shimazu,M, Matsuda,S, Wakabayashi,G, Tanabe,M, Hoshino,K, Kamei,S, Koyasu,S, Kitajima,M: "c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model"Wound Repair Regen. 10. 314-319 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto,S, Tanabe,M, Wakabayashi,G, Shimazu,M, Matsumoto,K, Kitahjima,M: "The Role of Tumor Ncrosis Factor-α and Interleukin- 1β in Ischemia-Reperfusion Injury of the Rat Small Intestine. Journal of Surgical Research, 99 : 134-141, 2001"J Surg Res. 99. 134-141 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato,Y, Shimazu,M, Walabayashi,G, Tanabe,M, Morikawa,Y, Hoshino,K, Harada,H, Kadomura,T, Obara,H, Urakami,H, Shinoda,M, Kitajima,M: "Significance of Portal Venous Flow in Graft Regeneration After Living Liver Transplantation"Transplant Proc. 33. 1484-1485 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanabe M, Shimazu M, Wakabayashi G, et al.: "Intraportal infusion therapy as a novel approach to adult ABO-incompatible liver transplantation"Transplantation. 73. 1959-1961 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawachi S, Shimazu M, Wakabayashi G, et al.: "Biliary complications in adult living donor liver transplantation with duct-to-duct hepaticocholedochostomy or Roux-en-Y hepaticojejunostomy biliary"Surgery. 132. 48-56 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinoda M, Shimazu M, Matsuda S, et al.: "c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model"Wound Repair Regen. 10. 314-319 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinoda M, Shimazu M, Wakabayashi G, et al.: "Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning"J Gastroenterol Hepatol. 17. 1211-1219 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida M, Wakabayashi G, Ishikawa H, et al.: "Arteriovenous shunting blood flow in the stomach is intravitally observed only ofter thermal injury in rats"Keio J Med. 51. 193-200 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Harada H, Wakabayashi G, Takayanagi A, et al.: "Transfer of the Interleukin-1 receptor antagonist gene into rat liver abrogates hepatic ischemia-reperfusion injury"Transplantation. 74. 1434-1441 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Obara H, Shimazu M, et al.: "Overexpression of Truncated IκBα Induces TNF-α-Dependent Apoptosis in Human Vascular Smooth Muscle Cells"Arteriosclerosis, Thrombosis, and Vascular Biology. 19. 2198-2204 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto S, Shimazu M, et al.: "The Role of Tumor Necrosis Factor-α amd Interleukin-1β in Ischemia-Reperfusin Injury of the Rat Small Intestine"Journal of Surgical Research. 99. 134-141 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 篠田 昌宏, 島津 元秀, ほか: "肝虚血再灌流障害に対するischemic preconditioning(IPC)とその機序"侵襲と免疫. 9. 18-23 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 篠田 昌宏, 島津 元秀, ほか: "各種病態に対する生体肝移植周術期におけるサイトカイン変動の検討"移植. 36. 159-165 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimazu M: "Trends in Gastroenterology and Hepatology"Ed. By Asakura H, Aoyagi Y and Nakazawa S, Springer Verlag. 370 (2001)

    • Related Report
      2001 Annual Research Report

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

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