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Combination therapy of beta2 -adrenoceptor activation and steroids for sepsis-induced renal injury

Research Project

Project/Area Number 25462832
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionTeikyo University

Principal Investigator

Nalkamura Akio  帝京大学, 医学部, 講師 (70266287)

Co-Investigator(Kenkyū-buntansha) 宮川 誠  帝京大学, 中央動物実験施設, 教務職員 (80398734)
Research Collaborator KUROSAKI Kumiko  
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords敗血症 / 腎傷害 / β2アドレナリン受容体 / グルココルチコイド / TNF-α / ヒストン / 腎機能 / TNF-α / ヒストン修飾 / ステロイド / 遺伝子導入 / 多臓器障害 / 副腎皮質ステロイド薬 / エピジェネテイクス / 腎臓 / TNFーα
Outline of Final Research Achievements

This study was undertaken to explore whether cross-talk between β2-adrenoceptor(β2-AR) and glucocorticoid may produce additive or even synergic anti-inflammatory effects, resulting in kidney protection against sepsis-induced acute kidney injury(AKI). Results demonstrated that administration of glucocorticoid in the kidney and renal cells with over-expression of β2-AR appeared to modulate renal dysfunction and inflammation following sepsis by altering cAMP-PKA, cannabinoid-1 and CD14-TLR4-TNF-α pathways. In addition, the combination therapy produced modulation of systemic nitric oxide and angiotensin II, and renal histone-modifying enzymes(HAT, HDAC, H3K9Ac), which further suppressed renal TNF-α gene transcription. Moreover, the combination therapy improved the survival of the rats exposed to sepsis-induced AKI. From these findings, the effect of β2-AR activation on glucocorticoid actions via TNF-α pathways was a critical effector in the host defense against sepsis-induced AKI.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2017 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Invited: 1 results)

  • [Journal Article] レニンアンジオテンシン系遺伝子多型と副腎ステロイド薬副反応との関係(Genotypes of the renin-angiotensin system and glucocorticoid complications)2015

    • Author(s)
      Akio Nakamura
    • Journal Title

      Pediatrics International

      Volume: 57 Issue: 1 Pages: 72

    • DOI

      10.1111/ped.12434

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 多臓器不全:敗血症腎傷害におけるβ2アドレナリン受容体(β2AR)活性の役割2017

    • Author(s)
      中村明夫
    • Organizer
      第44回日本集中治療医学会
    • Place of Presentation
      ロイトン札幌(北海道・札幌市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] β2-adrenoceptor (β2-AR)activation affords the kidney protection against sepsis-induced ARF.2017

    • Author(s)
      中村明夫、宮川誠
    • Organizer
      第44回日本集中治療医学会
    • Place of Presentation
      ロイトン札幌(北海道・札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 敗血症腎障害に対する副腎ステロイド薬を組み合わせたβ2アドレナリン受容体活性化療法2017

    • Author(s)
      中村明夫、宮川誠
    • Organizer
      第44回日本集中治療医学会
    • Place of Presentation
      ロイトン札幌(北海道・札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] CLP敗血症ラットモデルを用いたβ2交感神経受容体(β2AR)とステロイド併用治療の腎臓に対する組織化学的観点からの軽減効果2017

    • Author(s)
      宮川 誠、中村明夫
    • Organizer
      第44回日本集中治療医学会
    • Place of Presentation
      ロイトン札幌(北海道・札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] CLP敗血症ラットモデルにおけるβ2交感神経受容体とステロイド治療の腎臓に対する影響 -病理組織学的な検討-2015

    • Author(s)
      宮川 誠、黒崎くみ子、中村明夫
    • Organizer
      日本実験動物学会
    • Place of Presentation
      京都テルサ(京都・京都市南区東九条下殿田)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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