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Enhanced effect of recombinant human soluble thrombomodulin by ultrasound irradiation in acute liver failure

Research Project

Project/Area Number 17K17076
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Emergency medicine
Research InstitutionFukuoka University

Principal Investigator

Hoshino Kota  福岡大学, 医学部, 講師 (40762266)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords超音波 / 急性肝不全 / トロンボモジュリン / ソノポレーション / sonoporation / 効果増強 / Phosphatidylserine / 薬学
Outline of Final Research Achievements

This study aimed to determine the enhancement effect of US irradiation on recombinant human soluble thrombomodulin (rhsTM) in acute liver failure (ALF). rhsTM (1 mg/kg) and US (1 MHz, 0.3 W/cm2) were irradiated to the liver of lipopolysaccharide/D-galactosamine-induced ALF mice model. The post-treatment aspartate aminotransferase, alanine aminotransferase, and high-mobility group box 1 levels were significantly lower in the rhsTM + US group than in the rhsTM alone group. Histopathological findings revealed significantly reduced liver injury and apoptosis in the rhsTM + US group. By contrast, US irradiation had no effect on rhsTM and TNF-α concentration in the liver tissue. In conclusion, US irradiation enhanced the effect of rhsTM in the ALF mice model. However, further studies must be conducted to determine the exact mechanism of such enhancement effect.

Academic Significance and Societal Importance of the Research Achievements

本研究において、超音波照射がトロンボモジュリン製剤の効果を増強させる効果が認められた。トロンボモジュリン製剤は副作用である全身の出血合併症が問題となり、高用量の投与は危険である。そのため低用量のトロンボモジュリン製剤に超音波照射を加えることで、副作用のリスクを抑えた上で、効果を最大限に引き出すことができるため、理想的な治療法となる。
また、超音波はすでに日常診療で広く用いられているため、臨床への応用は極めて容易である。
さらには、他の薬剤にも応用できる可能性があり、超音波の新たな活用法を切り開いた意義ある研究である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2020 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Enhanced effect of recombinant human soluble thrombomodulin by ultrasound irradiation in acute liver failure2020

    • Author(s)
      Kota Hoshino
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: 10 Issue: 1 Pages: 1742-1742

    • DOI

      10.1038/s41598-020-58624-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 超音波照射によるトロンボモジュリン製剤の効果増強作用2019

    • Author(s)
      星野 耕大
    • Organizer
      第46回日本集中治療医学会学術集会
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Presentation] 超音波照射によるトロンボモジュリン製剤の効果増強作用2018

    • Author(s)
      星野 耕大
    • Organizer
      第28回日本超音波医学会九州地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] 急性肝不全モデルにおける超音波照射によるトロンボモジュリン製剤の効果増強作用2017

    • Author(s)
      星野 耕大
    • Organizer
      日本超音波治療研究会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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