Role of nitric oxide in the myocardial injury of myocarditis and myocardial ischemia

一氧化氮在心肌炎和心肌缺血心肌损伤中的作用

• 批准号: 08670828
• 负责人: NISHIKAWA Toshio
• 金额: $ 1.34万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670828/
• 关键词: 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

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.

本研究应用组织病理学、免疫组织化学、组织化学和分子生物学方法，探讨一氧化氮（NO）在心肌炎和心肌缺血心肌损伤中的作用。心肌炎大鼠血清和心肌组织中NO、TNF α和IL-1b含量明显升高，与心肌组织病理改变密切相关。诱导型一氧化氮合酶（iNOS）蛋白和mRNA在炎症损伤的巨噬细胞、内皮细胞和心肌细胞中呈强表达。用化学发光法和组织化学法大量检测了心脏中的超氧化物。免疫组化结果显示，心肌炎性病变中硝基酪氨酸呈阳性反应，提示过氧亚硝基阴离子参与了组织损伤。应用iNOS抑制剂氨基胍可明显抑制心肌炎大鼠心肌损伤的扩展，免疫组化显示冠状动脉结扎大鼠急性心肌梗死心肌呈iNOS阳性反应。心肌受累区硝基酪氨酸也呈阳性。结果提示，过量的NO在心肌炎和心肌缺血时心肌损伤的进展中起重要作用。

项目成果

Yoshinori Seko: "Expression of costimulatory molecules B7-1, B7-2, and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy." Circulation. 97. 637-639 (1998)

Yoshinori Seko：“共刺激分子 B7-1、B7-2 和 CD40 在急性心肌炎和扩张型心肌病患者心脏中的表达。”

Toshio Nishikawa: "Hypertrophic cardiomyopathy in Noonan Syndrome" Acta.Paediatr.Jpn.38. 91-98 (1996)

Toshio Nishikawa：“Noonan 综合征中的肥厚性心肌病”Acta.Paediatr.Jpn.38。

西川俊郎: "小児の不整脈源性右室心筋症の右室心筋組織像" 日本小児循環器学会雑誌. 13(2). 265 (1997)

Toshiro Nishikawa：“儿童致心律失常性右心室心肌病的右心室心肌组织学”日本小儿心脏病学会杂志 13（2）265（1997）。

Toshio Nishikawa: "Programmed cell death(apoptosis)in the myocardium with acute myocarditis." Microscopy Microanalysis. 3. 63-64 (1997)

Toshio Nishikawa：“急性心肌炎心肌中的程序性细胞死亡（细胞凋亡）。”

Toshio Nishikawa, et al.: "Programmed cell death (apoptosis) in the myocardium with acute myocarditis." Microscopy Microanalysis. 3(suppl 2). 63-64 (1997)

Toshio Nishikawa 等人：“急性心肌炎心肌中的程序性细胞死亡（细胞凋亡）。”