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Gene Therapy for Septic Shock with Altered Expression of G protein

Research Project

Project/Area Number 13671558
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

MATSUDA Naoyuki  HOKKAIDO UNIVERSITY, Hokkaido Univ., Grad. School of Med., Instructor (50332466)

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: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsSepsis / Shock / G protein / Gene Therapy / NF-KB / Gsタンパク / NF-κβ / 心室筋
Research Abstract

We used the rabbits and mice, which rendered sepsis by LPS injection or cecum ligation and puncture. Decreased expression of Gs α were reversed by steroid and by the gene therapy which used NF-kB decoy oligonucleotides (ODN) for the inhibition of transcriptional activity of NF-kB DNA region. In addition, we found radical scavenger could inhibit decreased expression of Gs α in septic rabbits. By these study process, high efficiency of transfection of NF-kB decoy oligonucleatides were found in lungs and atrial muscle.
Depended on NF-kB activity in atrial muscle, histamine plasma concentration, expressions of histamine receptor H_1 receptor and H_2 receptor found possibility to rise in sepsis shock. By a gene therapy of a NF-kB DON, we could completely restrain gene transcription of H_2 receptor and L-histidine decarboxylase in the atrium of septic rabbits
In addition, we merged acute lung injury for sepsis. Induction of a NF-kB decoy ODN may be available for new treatment of septic shock

Report

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

    (7 results)

All 2003 2002 Other

All Journal Article (5 results) Publications (2 results)

  • [Journal Article] Contractions to histamine in pulononary and mesenteric arferies from endotoxemic rabbits : modulation by vasclar expressions of ~.2003

    • Author(s)
      Matsuda N., et al.
    • Journal Title

      J Pharmacol Exp Ther 307

      Pages: 175-181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Normalization by edaravone a free radical scavenger of irraiation- reduced endothelial nitric oxide synthase expression.2003

    • Author(s)
      Zhang XH, Matsuda N, et al.
    • Journal Title

      Eur J Pharmacol 22

      Pages: 131-137

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] 敗血症性シヨックにおけるヒスタミンシグナルの役割2003

    • Author(s)
      松田直之, 服部裕一
    • Journal Title

      循環制御 24

      Pages: 118-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Hemodynamic Significance of histamine synthesis and histamine Hi and H_2-receptor gene expression during endotoxemia.2002

    • Author(s)
      Matsuda N., et al.
    • Journal Title

      Naunyn-Schmiedeberg's Arch Pharmacol 366

      Pages: 513-521

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] 心筋細胞におけるGTP結合蛋白質の循環制御機構-循環器病態における最近の知見-2002

    • Author(s)
      松田直之, 服部裕一
    • Journal Title

      循環制御 23

      Pages: 171-179

    • NAID

      10012614583

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuda N et al.: "Hemodynamic significance of histamine synthesis and Histamine H_1-and H_2 receptor gene expression during endotaxemia"Naunyn-Schmiedeberg's Archives of pharmacology. 366. 513-521 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松田直之: "心筋細胞におけるGTP結合蛋白質の循環制御機構"循環制御. 23. 171-179 (2002)

    • Related Report
      2002 Annual Research Report

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

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