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

本研究通过组织病理学、免疫组织化学、组织化学和分子生物学等方法，探讨一氧化氮(NO)在心肌炎心肌损伤和心肌缺血发病机制中的作用。大鼠心肌炎时，血清和心脏组织中NO含量明显升高，而TNFa和IL-1b含量则明显升高，且与心肌组织病理改变密切相关。炎性病变的巨噬细胞、血管内皮细胞和心肌细胞表达诱导型一氧化氮合酶(INOS)蛋白和mRNA。用化学发光法和组织化学方法在心脏中检测到大量的超氧化物歧化产物。免疫组织化学检查显示心肌炎性病变中硝基酪氨酸呈阳性反应，提示过氧亚硝酸盐参与了组织损伤。INOS抑制剂氨基胍对心肌炎大鼠心肌损伤有明显的抑制作用。冠状动脉结扎大鼠急性心肌梗死后，免疫组织化学显示iNOS呈阳性反应。心肌受累部位硝基酪氨酸也呈阳性反应。这些结果提示，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。

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.