| Project/Area Number |
15590582
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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 |
Legal medicine
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
KURISAKI Emiko (2004) Fukushima Medical University, Dept of Legal Medicine, Lecturer, 医学部, 講師 (30106356)
郡司 啓文 (2003) 福島県立医科大学, 医学部, 講師 (20234643)
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| Co-Investigator(Kenkyū-buntansha) |
ADACHI Junko Kobe University, Graduate School of Medicine, Associate professor, 大学院・医学研究科, 助教授 (40030887)
栗崎 恵美子 福島県立医科大学, 医学部, 講師 (30106356)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | ischemia / repeefusion / shock / nitric oxide synthase (NOS) / superoxide / cholesterol peroxides / histochemistry / HPLC / HPLC / 緊縛性ショック / 過酸化ストレス / 遠隔臓器 / 免疫組織化学 / 一酸化窒素代謝物濃度 / Nitric Oxide Synthase(NOS) / NOS阻害薬 |
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| Research Abstract |
To clarify the role of superoxide (O_2-) produced by NOS after ischemia/reperfusion (I/R), a hind limb tourniquet ischemia animal model was used. A rubber band was applied to the inguinal region of the hind limb for 3 hours under isoflurane anesthesia followed by reperfusion. O_2- production in skeletal muscle cells was observed in mice using an in situ detection technique with hydroethidine. Five minutes after the start of reperfusion, burst production of O_2- was detected in the cytoplasm as well as on and/or near the membrane of muscle cells subjected to I/R. Remarkably increased NADPH diaphorase activiry, and immunoreactivities using an anti-NOS antibody and anti-4-hydroxy-nonenal (HNE) antibody were also observed in I/R muscle, whereas there was no significant increase of immunoreadrivity using anti-nitrotyrosine (NT). These findings suggested that O_2- production by NOS as well as xanthine oxides was involved in the mechanism of O_2- production after reperfusion. Positive imunoreactivity using anti-HNE was observed in the liver and the kidney and immunoreactivity using anti-NT was positive in the heart after reperfusion. Cholesterol peroxides and NO metabolites were determined by HPLC. Levels of cholesterol peroxides increased in the muscle subjected to I/R and in the kidney after reperfusion. Levels of NO metabolites in plasma also increased between 15 and 60 min after reperfuiion. HPLC results were consistent with histochemical findings. These results suggested that O2-and/or NO produced by NUS was responsible for not only local injury but also remote organ injury after I/R. In the present study, we showed that O_2- production by NOS plays a role as an initiator of the development of shock after I/R.
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