| Project/Area Number |
16K11394
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Sepsis / MODS / PAR2 blockade / VEGF / mechanism / PAR2 blochade |
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| Outline of Final Research Achievements |
In our experiment, it seems that three hours treatment of PAR2 blockade is effective in acute sepsis for the improvement and arrest of multiple organ dysfunction syndrome (MODS) in sepsis through modulation of VEGF system. Indeed, in our research over last decade we found that PAR2 is a critical player and trigger for MODS in sepsis, in some cases equally important as of TNF-alpha. This PAR2 is closely associated with angiogenic system (VEGF), endothelin (ET) and inflammatory (TNF) cascade from the early hours of sepsis in connection to MODS development and progression. From in vitro studies, using
cardiomyocytes and lung macrophages, we also confirmed the relation between VEGF and PAR2 in LPS administered cells using PAR2 blocker and using VEGF antagonist. From our series of experiments, now we can conclude that PAR2 inhibition from early hours of sepsis might be effective in the treatment and prevention of lung injury and myocardial dysfunction through amelioration of VEGF signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究は敗血症の治療と予防のために行った研究である。敗血症及び重症敗血症（感染に起因する二次的な急性臓器不全）また敗血症ショック（輸液負荷によって回復しない低血圧を伴う重症敗血症）は、毎年世界中で2700万人が罹患し、その４人に１人以上が死亡すると報告されている。この研究の結果は、敗血症及び敗血症によって起こる臓器障害の改善につながると考えられ、死亡率の現象及び後遺症の改善、医療コストの削減に繋がるなど非常に社会的に意義があると考える。
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