一氧化氮在实验性NIDDM大鼠心肌病变中的变化

Changes of ultrastructure and level of nitric oxide in the myocardium of rats with experimental non-insulin-dependent diabetes mellitus

目的 :用非胰岛素依赖型糖尿病 (NIDDM)模型 ,研究一氧化氮 (NO)、构建型一氧化氮合酶 (cNOS)与NIDDM早期心肌病关系。方法 :给大鼠尾静脉注射小剂量链尿佐菌素 ,使大鼠糖耐量异常 ,然后加喂高热量食物 ,引起大鼠肥胖 ,饲养 8周 ,可形成类似NIDDM模型。观察实验性NIDDM大鼠心肌超微结构、心肌NO产物NO-2 /NO-3 、cNOS表达的变化。结果 :①透射电镜观察发现 ,NIDDM大鼠心肌有超微结构改变 ,例如 :线粒体肿胀、心肌闰盘间隙增宽。②NIDDM大鼠心肌组织NO-2 /NO-3 水平显著低于正常对照大鼠 (P <0 .0 1) ,L -精氨酸组心肌组织NO-2 /NO-3显著高于NIDDM组 (P <0 .0 1)。③NIDDM大鼠心肌组织cNOSmRNA表达显著低于正常对照大鼠 (P <0 .0 1)。结论 :NIDDM早期存在心肌病变 ,NO与其发生机制有关 ,L

AIM:The ultrastructure,the levels of NO - 2/NO - 3 were investigated in the myocardium of rats with non-insulin dependent diabetes mellitus. METHODS: In order to establish a model of non-insulin dependent diabetes mellitus (NIDDM), we injected rats with small dose streptozocoi (iv). Two weeks after the injection, the rats developed impaired glucose tolerance. Then, they were fed with high energy diet for eight weeks to form NIDDM. RESULTS: (1) The ultrastructures of cardiac myocytes of NIDDM rats were changed evidently, with swelled mitochondrion and widened intercalated-disk gap; (2) The levels of NO - 2/NO - 3 in the heart tissue of NIDDM rats were significantly lower than those of normal rats( P< 0.01), then the levels of NO - 2/NO - 3 in L-arginine group were obviously higher than those in NIDDM group.( P< 0.01); (3) The levels of cNOS mRNA in the heart tissue of NIDDM rats were significantly lower than those of normal rats.( P< 0.01). CONCLUSION: There exists myocardiopathy at the early stage of NIDDM, and the functional down-regulation of NO system in cardiac myocyte might be linked with pathology of myocardiopathy in NIDDM. L-arginine can significantly up-regulate NO - 2/NO - 3 level in NIDDM group.