| Project/Area Number |
07457145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Fukui Medical University |
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Principal Investigator |
MATSUKAWA Shigeru Fukui Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00092809)
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| Co-Investigator(Kenkyū-buntansha) |
AMESHIMA Shingo Fukui Medical University, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (60262614)
ISHIZAKI Takehsi Fukui Medical University, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (80151364)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | NO related radicals / O_2- / Acute lung injury / Xanthine oxidase / 摘出かん流肺 / 高濃度酸素 / NOドナー / かん流液LDH活性 / 肺湿 / 乾重量 / NO_<2-> / NO_<3-> / ONOO^- / Leukotoxin / Nitric oxide / 血管内皮細胞 |
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| Research Abstract |
We wondered if leukotoxin (Lx), an epoxide of linolate, which activated vascular endothelial nitric oxide synthase, could affected redox ballance and could produce O_2-. We wondered then if acute lung injury could occured by the treatment of hyperoxia and NO.To clarify these question we attemped to the experiment by using isolated perfused rat lungs (IPRL) and human cultured pulmonary artery endothelium (HPAE). Lx at 30 mumol suppressed mitochondrial respiration, cytochrome C oxidase activity and content of ATP,NADH and GSH in lungs. There was no changes of NAD,NADP,or GSSG contents. Since such suppressive effect of Lx was attenuated in the presence of LNMMA or SOD but not DNMMA,Lx seemed to affect energy metabolism and redox state of lungs via mechanisms related to NO or NO-related radicals. When IPRL were ventilated with air containing different concentration of oxygen and perfused with solution containing with different doses of NO donor (NOC7), 40%O_2+NOC7 100muM treated lungs caused at most increase in lung wet weght/dry weight and perfusate LDH activity. It suggested some critical molar ratio of NO and O_2- may cause acute edemagenic lung injury. Lx dose-dependently stimulated O_2- production of HPAE which was suppressed by allopurinol but not by indomethacin, apocinin, SOD,or LNMMMA,indicating activation of xanthine oxidase of HPAE.Since Lx has been a substance causing Acute Respiratory Distress Syndrome (ARDS), our current study suggests an important pathophysiological role of NO related radicals in acute lung injury.
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