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肺塞栓症の病態である白血球・血小板凝集反応のRNA干渉法を用いたメカニズム解明

Research Project

Project/Area Number 17659492
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

溝部 俊樹  京都府立医科大学, 医学研究科, 講師 (50239266)

Co-Investigator(Kenkyū-buntansha) 中嶋 康文  京都府立医科大学, 医学研究科, 助教 (70326239)
影山 京子  京都府立医科大学, 医学研究科, 助教 (80347468)
谷口 知史  京都府立医科大学, 医学研究科, 助教 (70398402)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords遺伝子治療 / RNAi法 / 血液細胞 / 炎症 / 凝固 / 相互作用 / 肺梗塞 / 白血球 / 血小板 / Tissue Factor
Research Abstract

前年度において、我々は膝関節全景換手術症例を対象にした臨床実験により、Flow-Cytometry法,ELISA法,Whole Blood Impedance法等を用いて、下半身から還流された下大静脈内において、白血球(主に単球)、血小板、血管内皮細胞が相互作用を及ぼし互いに活性化される事によりLeukocyte-Platelet Conjugate, Microparticleの形成Tissue Factor, CD40Ligand等サイトカインの産生か行われ、それらがFibrin MonomerComplexの生成及び血液凝固亢進を引き起こす事を明らかにし、肺梗塞発生との関係を示唆した。それらの主な結果は、論文として本年度に公表した。(J Throrab Haemost.2007Apr;5(4):738-45,)本年度は、更にこれら血液細胞の相互作用のメカニズムをIn Vitroにおいて観察すべく、培養細胞、及びPrimary Cellを用いてRNAi法による遺伝子ノックダウンにより白血球-血小板間の相互作用が弱められることを明らかにした。具体的には、THP-1細胞及びヒト単球表面抗原のCD162(P-selectin glycoprotein-1),またはCD40をNucleofection法を用いてsiRNAを導入し、72時間後に表面抗原がノックダウンされていることを確認した細胞と血小板を共培養して、Leukocyte-Platelet Congugate産生の低下、Soluble Tissue Factor、CD142発現の低下、Microparticle産生の低下を確認した。また、血小板機能も抑制されることを確認した。

Report

(2 results)
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (8 results)

All 2007 2006 2005 Other

All Journal Article (8 results)

  • [Journal Article] Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty.2007

    • Author(s)
      Kageyama K, Nakajima Y et al.
    • Journal Title

      Journal of Thrombosis and Haemostasis 5,4

      Pages: 738-745

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Predictors of atrial fibrillation after off-pump coronary artery bypass graft surgery.2007

    • Author(s)
      Hosokawa K, Nakajima Y et al.
    • Journal Title

      British Journal of Anaesthesia (In Press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dietary-induced thermogenesis and perioperative thermoregulation2007

    • Author(s)
      Mizobe T, Nakajima Y
    • Journal Title

      Masui 56,3

      Pages: 305-316

    • NAID

      40015345753

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Perioperative amino acid infusion improves recovery and shortens the duration of hospitalization after off-pump coronary artery bypass grafting.2006

    • Author(s)
      Umenai T, Nakajima Y et al.
    • Journal Title

      Anesthesia and Analgesia 103, 6

      Pages: 1386-1393

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evaluation of residual shunt flow of coronary artery fistulae by intra-operative transoesophageal echocardiography.2006

    • Author(s)
      Hosokawa K, Nakajima Y et al.
    • Journal Title

      Anaesthesia 61, 8

      Pages: 814-815

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fructose administration increases intraoperative core temperature by augmenting both metabolic rate and the vasoconstriction threshold.2006

    • Author(s)
      Mizobe T, Nakajima Y et al.
    • Journal Title

      Anesthesiology 104, 6

      Pages: 1124-1130

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clonidine produces a dose-dependent impairment of baroreflex-mediated thermoregulatory responses to positive end-expiratory pressure in anaesthetized humans.2005

    • Author(s)
      Mizobe T et al.
    • Journal Title

      Br J Anaesth. 94(4)

      Pages: 536-541

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fructose Administration Augments Metabolic Rate and the Vasoconstriction Threshold, Thus Increasing Intraoperative Core Temperature

    • Author(s)
      Mizobe T et al.
    • Journal Title

      Anesthesiology (In press)

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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