| Project/Area Number |
07671682
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
KUBOTA Tatsuya Jichi medical school medicine, Professor, 医学部, 教授 (90048992)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUYAMA Naohiro Jichi medical school medicine, Assistant, 医学部, 助手 (90265273)
WADA Masahiko Jichi medical school medicine, Assistant, 医学部, 助手 (10240558)
OHTAKE Kazue Jichi medical school medicine, Associate Professor, 医学部, 助教授 (00092156)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Endotoxin shock / Neutrophil elastase / Endothelial cell damage |
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| Research Abstract |
To clarify the role of the neutrophil elastase in the endotoxin shock we studies the effects of the neutrophil elastase inhibitor (ONO-5046 : a competitive, reversible and specific human neutrophil elastase inhibitor with a molecular weight of 456.5) on endotoxin shock models in dogs. The pre-treatment of ONO-5046 attenuated the endothelial cell damage caused by neutrophil elastase on the endotoxin shock model in dog. ONO-5046 did not prevent themigration of neutrophils, but prevented a significant reducation in platelets and AT-III.These effects were not observed in post-treatment model. Platelets and AT-III showed lowest levels within 60 minutes after endotoxin administration. Consequently, endothelial damage has already occurred on the post-treatment study. However, from the observation of significant decreases in 6-ketoPGF_1 alpha and CH_<50> consumption, the post-treatment of ONO-5046 appear to attenuate endothelial damage caused by neutrophil elastase.
We concluded that neutrophil elastase is one of the main factors on the injury of endothelium in the endotoxin shock model in dog.
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