Marfella Raffaele, Di Filippo Clara, Esposito Katherine, Nappo Francesco, Piegari Elena, Cuzzocrea Salvatore, Berrino Liberato, Rossi Francesco, Giugliano Dario, D'Amico Michele
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy.
Diabetes. 2004 Feb;53(2):454-62. doi: 10.2337/diabetes.53.2.454.
We investigated the role of inducible nitric oxide synthase (iNOS) on ischemic myocardial damage and angiogenic process in genetically deficient iNOS (iNOS(-/-)) mice and wild-type littermates (iNOS(+/+)), with and without streptozotocin-induced (70 mg/kg intravenously) diabetes. After ischemia (25 min) and reperfusion (120 min), both iNOS(+/+) and iNOS(-/-) diabetic mice (blood glucose 22 mmol/l) had myocardial infarct size greater than their respective nondiabetic littermates (P < 0.01). Myocardial infarct size (P < 0.05), apoptotic index (P < 0.005), and tissue levels of tumor necrosis factor (P < 0.01), interleukin-6 (P < 0.01), and interleukin-18 (P < 0.01) were higher in nondiabetic iNOS(-/-) mice compared with nondiabetic iNOS(+/+) mice. As compared with diabetic iNOS(-/-) mice, diabetic iNOS(+/+) mice showed a greater infarct size (P < 0.01) associated with the highest tissue levels of nitrotyrosine and proinflammatory cytokines, as well as apoptosis. The beneficial role of iNOS in modulating defensive responses against ischemia/reperfusion injury seems to be abolished in diabetic mice.
我们研究了诱导型一氧化氮合酶（iNOS）在基因缺陷型iNOS（iNOS(-/-)）小鼠和野生型同窝小鼠（iNOS(+/+)）的缺血性心肌损伤和血管生成过程中的作用，这些小鼠分为有和没有链脲佐菌素诱导（静脉注射70 mg/kg）糖尿病的两组。在缺血（25分钟）和再灌注（120分钟）后，iNOS(+/+)和iNOS(-/-)糖尿病小鼠（血糖22 mmol/l）的心肌梗死面积均大于各自的非糖尿病同窝小鼠（P < 0.01）。与非糖尿病iNOS(+/+)小鼠相比，非糖尿病iNOS(-/-)小鼠的心肌梗死面积（P < 0.05）、凋亡指数（P < 0.005）以及肿瘤坏死因子（P < 0.01）、白细胞介素-6（P < 0.01）和白细胞介素-18（P < 0.01）的组织水平更高。与糖尿病iNOS(-/-)小鼠相比，糖尿病iNOS(+/+)小鼠表现出更大的梗死面积（P < 0.01），伴有最高水平的硝基酪氨酸和促炎细胞因子以及凋亡。iNOS在调节对缺血/再灌注损伤的防御反应中的有益作用在糖尿病小鼠中似乎被消除了。
