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TNF-α a antisense transfer improves ischemia / reperfusion injury of the hepatic graft

Research Project

Project/Area Number 08407031
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SUGIMACHI Keizo  Kyushu University, Graduate School of Medical Scienccs, Department of Surgery and Science, Professor, 医学系研究科, 教授 (00038762)

Co-Investigator(Kenkyū-buntansha) NISHIZAKI Takashi  Kyusyu University, Graduate School of Medical Sciences, Department of Surgery and Science, Research Associate, 医学部・附属病院, 助手 (70253416)
YANAGA Katsuhiko  Kyusyu University, Graduate School of Medical Sciences, Department of Surgery and Science, instructor, 医学部・附属病院, 講師 (70220176)
野本 健一  九州大学, 大学院・医学系研究科, 助手 (50315090)
Project Period (FY) 1996 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥40,100,000 (Direct Cost: ¥40,100,000)
Fiscal Year 1999: ¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 1998: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1997: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1996: ¥14,200,000 (Direct Cost: ¥14,200,000)
Keywordscold ischemia / reperfusion injury / liver transplantation / HVJ-CL / TNF-α antisense / Kupffer cells / oligodeoxynucleotides / IL-1β / TNF-α / 冷虚再潅流障害 / 遺伝子導入 / TNFα / NF-κB / decov / 肝臓移植 / 冷虚血再潅流障害 / NF-κ B decoy / 冷虚血再潅流傷害 / Apoptosis
Research Abstract

Cold ischemia/reperfusion injury of the hepatic graft, an unsolved problem in liver transplantation that has been attributed to the release of inflammatory cytokines from activated Kupffer cells. We recently designed a novel vehicle composed of cationic liposomes fused with hemagglutinating virus of Japan (HVJ), namely HVJ-cationic liposomes (HVJ-CL), and using this vector system, we assessed the cytotoxicity, efficiency of Fluorescein isothiocyanate (FITC)-labeled oligodeoxynucleotides (FITC-ODNs) delivery to Kupffer cells and effects of TNF-α antisense delivery against ischemia/reperfusion injury in a rodent hepatic graft. FITC signals were recognized in over 95% of ED2-positive Kupffer cells of transplanted liver 4hrs after FITC-ODNs transfer. The transfer efficiency (18.5 ± 3.1%) using HVJ-CL applied at one-eighth the amount of HVJ and lipids of conventional HVJ-liposomes (HVJ-L) was much higher than that achieved by HVJ-L (10.4 ± 1.2%, p<0.01), while there was no signincant difference in the vector-induced release of cytosolic enzymes from hepatocytes into the blood circulation between HVJ-CL and HVJ-L groups. Treatment with TNF-α antisense transfer significantly suppressed the release of cytosolic enzymes from hepatocytes, the serum levels of TNF-α and immunohistochemical expression of TNF-α by Kupffer cells 4hrs after liver transplantation. This HVJ-CL method provides a safe and effective ODNs delivery to Kupffer cells of hepatic grafts in rats

Report

(5 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 橋元 宏治、他: "Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation."Transplantation. 70. 1318-1322 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 池上 徹、他: "Experiment study of the effects of deletion variant hepatocyte growth factor on hepatic ischemia-reperfusion injury."British journal of Surgery. 87. 59-64 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 内山 秀樹、他: "Effects of deletion variant of hepatocyte growth factor on reduced-size liver transplantation in rats."Transplantation. 68. 39-44 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 副島 雄二、他: "Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation."Journal of Surgical Reserch. 86. 150-154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 池上 徹、他: "Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats."Surgery. 125. 602-607 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 西崎 隆、他: "Intraoperative hyaluronic acid clearance predicts postoperative graft function in living related liver transplantation."Int Surgery. 84. 143-146 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hashimoto K., Nishizaki T., Yoshizumi T., Uchiyama H., Okano S., Ikegami T., Yanaga K., Sugimachi K.: "1. Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation."Transplantation. 70. 1318-1322 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikegami T., Nishizaki T., Uchiyama H., Hashimoto K., Yanaga K., Sugimachi K.: "2. Experiment study of the effects of deletion variant hepatocyte growth factor on hepatic ischemiareperfusion injury."Br J Surg. 87. 59-64 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchiyama H., Yanaga K., Nishizaki T., Soejima Y., Yosshizumi T., Sugimachi K.: "3. Effects of deletion variant of hepatocyte growth factor on reduced-size liver transplantation in rats."Transplantation. 68. 39-44 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Soejima Y., Yanaga K., Nishizaki T., Yoshizumi T., Uchiyama H., Sugimachi K.: "4. Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation."Journal of Surgical Research.. 86. 150-154 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikegami T., Nishizaki T., Uchiyama H., Kakizoe S., Yanaga K., Sugimachi K.: "5. Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats."Surgery. 125. 602-607 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishizaki T., Okano S., Uchiyama H., Ikegami T., Hashimoto K., Minagawa R., Ota R., Nomoto K., Yanaga K., Sugimachi K.: "6. Intraoperative hyaluronic acid clearance predicts postoperative graft function in living related liver transplantation."Int Surg.. 84. 262-265 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suehiro T., Boros P., Emre S., Sheiner PA., Guy S., Schwartz Me., Miller CM.: "7. Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early glaft function in liver transplantation."Transplant Int. 11. 143-146 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshizumi T., Yanaga K., Soejima Y., Maeda T., Uchiyama H., Sugimachi K.: "8. Amelioration of liver injury by ischaemic preconditioning"Br J Surg. 85. 1636-1640 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wakiyama S., Yanaga K., Soejima Y., Nishizaki T., Sugimachi K.: "9. Significance of donor nutritional status on rewarming injury of hepatic allograft in rat"Eur Surg Res. 29. 339-345 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wakiyama S., Yanaga K., Soeiima Y., Nishizaki T., Sugimachi K.: "10. Reduction of rewarming injury of the hepatic graft by a heat insulator."Br J Surg. 84. 459-463 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary

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Published: 1996-04-01   Modified: 2016-04-21  

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