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遺伝子を用いた放射線肺臓炎に対する新しい治療法

Research Project

Project/Area Number 15659285
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionTokai University

Principal Investigator

福山 直人  東海大学, 医学部, 講師 (50349338)

Co-Investigator(Kenkyū-buntansha) 辻 千鶴子  東海大学, 医学部, 講師 (80130079)
中澤 博江  東海大学, 医学部, 教授 (20110885)
玉井 好史  東海大学, 医学部, 講師 (90207225)
盛 英三  国立循環器病センター研究所, 心臓生理部, 部長 (90146598)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords急性肺障害 / ウイルスベクター / アポトーシス / 放射線肺臓炎 / 遺伝子導入 / 遺伝子治療
Research Abstract

昨年度は予定通りに1.遺伝子導入のためのイオン化ゲルの作成、2.肺胞マクロファージへの遺伝子導入法の確立、3.アデノウイルスベクターとの遺伝子導入効率の比較、4.遺伝子発現期間の検討を行い、イオン化ゲルを用いることにより肺胞マクロファージに遺伝子を導入することが可能であり、遺伝子導入期間が4週間であることが確認できた。本年度はその基礎実験を基にin vivoにおける遺伝子導入や遺伝子発現期間の検討を行った。
(1)遺伝子導入や遺伝子発現期間の検討(in vivo)
レポーター遺伝子として、β-galactosidase(LacZ)遺伝子をイオン化ゲルに吸着させラットに吸入療法を施行し、肺組織内に遺伝子が導入されるかどうか遺伝子導入後LacZ染色にて確認した。LacZ染色及び各種細胞の特殊免疫染色を二重染色で施行したところ、遺伝子発現は主に肺胞マクロファージに認められたが、その遺伝子発現期間はin vitroの結果とは異なり、約7日間と短いことが確認された。その理由として、遺伝子導入肺胞マクロファージにおいてCytochrome C染色が陽性であることから、遺伝子導入をすることにより肺胞マクロファージがアポトーシスを引き起こしていることが考えられた。
(2)抗線維化遺伝子導入による治療効果の検討
ラット放射線照射モデルにリニアック20Gの線量を7分間片肺に照射するモデルを使用し、抗線維化遺伝子を導入することによる治療効果の検討を行った。抗線維化遺伝子をイオン化ゲルに吸着させ吸入療法を行うことにより、放射線肺照射による急性肺障害を抑制することが気管支肺胞洗浄のみならず組織化学的にまたCT所見においても明らかとなった。
以上のようにほぼ予定通りに実験を終了し、極めて有用な結果を得、現在学術誌に投稿中である。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (18 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (6 results)

  • [Journal Article] Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet.2005

    • Author(s)
      Chen, Y
    • Journal Title

      Biochem Biophys Res Commun 326(1)

      Pages: 45-51

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of enhanced sensitivity of NMDA recptors in vulnerability of developing cortical neurons to mrthylmercury neurotoxicity.2004

    • Author(s)
      Miyamoto K
    • Journal Title

      TOXICOLOGY AND APPLIED PHARMACOLOGY 197(3)

      Pages: 321-321

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Peroxynitrite, a product between nitric oxide and superoxide anion, plays a cytotoxic role in the development of post-bypass systemic inflammatory response.2004

    • Author(s)
      Hayashi Y
    • Journal Title

      EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 26・(2)

      Pages: 276-280

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cell therapy for pulmonary hypertension : What is the true potential of end othelial progenitor cells? Response.2004

    • Author(s)
      Nagaya N
    • Journal Title

      CIRCULATION 109・(12)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes.2003

    • Author(s)
      Hayashi Y
    • Journal Title

      J Thorac Cardiovasc Surg 126・(6)

      Pages: 1813-1821

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibition of nitrotyrosine formation reduces endotoxin-induced liver injury irrespective of TNF-α.2003

    • Author(s)
      Hoshiai K
    • Journal Title

      J Clin Biochem Nutr 33

      Pages: 61-67

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anti-inflammatory effect of Pelteobagrus nudiceps extract on rat model of CFA-induced pulmonary tuberculous granuloma.2003

    • Author(s)
      Shoyama, Y
    • Journal Title

      Pathophysiology 9・(2)

      Pages: 89-95

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Myeloperoxidase has directly-opposed effects on nitration reaction-study on myeloperoxidase-deficient patient and myeloperoxidase-knockout mice.2003

    • Author(s)
      Ichimori, K
    • Journal Title

      Free Radic Res. 37・(5)

      Pages: 481-489

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hybird cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells.2003

    • Author(s)
      N.Nagaya
    • Journal Title

      Circulation. 108・(7)

      Pages: 889-895

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Quercetin, a natural flavonoid, attenuates vacuolar formation in the optic tract in rat chronic cerebral hypoperfusion model.2003

    • Author(s)
      Takizawa S
    • Journal Title

      Brain Res 980・(1)

      Pages: 156-160

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reperfusion enhances nitrotyrosine formation in rat focal cerebral ischemia.2003

    • Author(s)
      Takizawa S
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases 12・(4)

      Pages: 196-200

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of vascular endothelial growth factor by fibrin as a dermal substrate for cultured skin substitute.2003

    • Author(s)
      Hojo M
    • Journal Title

      Plast Reconstr Surg 111・(5)

      Pages: 1638-1645

    • Related Report
      2004 Annual Research Report
  • [Publications] Hayashi, Y., Y.Sawa, N.Fukuyama, et al.: "Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes"J Thorac Cardiovasc Surg. 126・6. 1813-1821 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hojo, M., S.Inokuchi, M.Kidokoro, N.Fukuyama, et al.: "Induction of vascular endothelial growth factor by fibrin as a dermal substrate for cultured skin substitute."Plast Reconstr Surg. 111・5. 1638-1645 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ichimori, K., N.Fukuyama, H.Nakazawa, et al.: "Myeloperoxidase has directly-opposed effects on nitration reaction--study on myeloperoxidase-deficient patient and myeloperoxidase-knockout mice."Free Radic Res. 37・5. 481-489 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kasahara, H., E.Tanaka, N.Fukuyama, et al.: "Biodegradable gelatin hydrogel potentiates the angiogenic effect of fibroblast growth factor 4 plasmid in rabbit hindlimb ischemia."J Am Coll Cardiol. 41・6. 1056-1062 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagaya, N., K.Kangawa, M.Kanda, M.Uematsu, T.Horio, N.fukuyama, et al.: "Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells."Circulation. 108・7. 889-895 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shoyama, Y., C.Tsuji, S.Shioya, N.Fukuyama, H.Nakazawa: "Anti-inflammatory effect of Pelteobagrus nudiceps extract on rat model of CFA-induced pulmonary tuberculous granuloma."Pathophysiology. 9・2. 89-95 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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