| Project/Area Number |
08670828
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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 |
Circulatory organs internal medicine
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
NISHIKAWA Toshio Tokyo Women's medical University, Associate Professor, 医学部, 助教授 (50120019)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Ikuo Tokyo Women's medical University, Assistant, 医学部, 助手 (30266712)
ANDO Akiko Tokyo Women's medical University, Assistant, 医学部, 助手 (90232090)
MASUDA Akihiro Tokyo Women's medical University, Associate Professor, 医学部, 助教授 (60209434)
KASAJIMA Takeshi Tokyo Women's medical University, Professor, 医学部, 教授 (30045653)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Myocarditis / myocardial ischemia / rat / nitric oxide / iNOS / cytokine / immunohistochemistry / molecular biology / 梗塞境界領域 / peroxynitrite / 心筋傷害 / アミノグアニジン / 活性酸素 / 心筋障害 / cytokine |
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| Research Abstract |
This study was designed to investigate the role of nitric oxide (NO) in the pathogenesis of myocardial injury in myocarditis and myocardial ischemia by the methods of histopathology, immunohistochemistry, histochemistry and molecular biology. The amount of NO was distinctively increased in the serum and the heart tissue as well as that of TNFa and IL-1b in association with the severe histopathologic findings of the myocardium in rat myocarditis. Inducible NO synthase (iNOS) protein and mRNA were strongly expressed in the macrophage, endotheium and myocardial cells in the inflammatory lesion. Superoxide was massively detected in the heart by the methods of chemiluminescence and histochemistry. Immunohistochemical examination revealed positive reactivity for nitrotyrosine in the inflammatory lesion of the myocardium, suggesting that peroxynitrite contributes to the tissue damage. The extension of myocardial injury was significantly inhibited in the myocarditis rat administered with aminoguanidine, an inhibitor of iNOS.The myocardium with acute infarction from rat with coronary artery ligation showed positive reactivity for iNOS by the method of immunohistochemistry. Nitrotyrosine was also positive in the affected area of the myocardium. These results suggest that excess amount of NO plays an important role in the progression of myocardial injury in myocarditis and myocardial ischemia.
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