| Project/Area Number |
11470270
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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 |
Thoracic surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
WADA Hiromi Graduate School of Medicine, Kyoto University, Professor, 医学研究科, 教授 (90167205)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hajime Insritute for Virus Research, Kyoto University, Assistante Professor, ウイルス研究所, 助手 (70303914)
TOYOKUNI Shinya Graduate School of Medicine, Kyoto University, Associate Professor, 医学研究科, 助教授 (90252460)
KONDO Hirosato Japan Oreganan Company Institute for Medicire, Head of departed, 医薬研究所, 化学研究室長
平田 敏樹 京都大学, 大学院・医科学研究所, 助手 (70281110)
福瀬 達郎 京都大学, 大学院・医科学研究所, 助手 (90263152)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | ischemia-reperfusion injury / Selection blocken / reactive oxygen species / DNA damage / 8-OHdG(8-hydroxy-2'-deoxyguanosine) / oxidative stress / MPO / 肺移植 / ADF / Thioredoxin / Thioredoxine |
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| Research Abstract |
Importance of reactive oxygen species released through interaction of leukocyte-endothelial cell in ischemia-reperfusion injury of the lung is not yet fully understood. A novel selectin blocker OJ-R9188, which inhibits the interaction may alleviate oxidative stress and pulmonary dysfunction after warm ischemia reperfusion. Rat lungs were reperfused at 37℃ for 60 min with an ex vivo model, and were divided into three groups (n=10). In Fresh group, lungs were reperfused immediately after harvest. In OJ-R (-) and OJ-R (+) groups, lungs were reperfused after warm ischemia at 37℃ for 90 min. In OJ-R (+) group, rats received 100 μg/body of OJ-R9188 intravenously 10 min before the harvest. Electron spin resonance method was used to assess the direct scavenging activity of OJ-R9188. Both shunt fractions and wet/dry weight ratios of the lung tissue after reperfusion in OJ-R (+) group were significantly lower than those in OJ-R (-) group. Oxidative DNA damage in the alveolar wall of OJ-R (+) group, assessed by immunohistochemical quantitation of 8-hydroxy-2'deoxyguanosine, was significantly lower than that of OJ-R (-) group. Immunostaining of 3-nitro-L-tyrosine, which represents nitric oxide-mediated oxidative damage, was also more intense in OJ-R (-) group than in OJ-R (+) group. Direct scavenging activity of OJ-R9188 was not observed, and the number of leukocytes infiltrated to the lung tissue as seen by myeloperoxidase activity was not different between OJ-R (-) and OJ-R (+) groups. A novel selectin blocker OJ-R9188 improves pulmonary function after warm ischemia-reperfusion and alleviates reperfusion-induced oxidative alveolar damage.
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