Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice
Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice
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DOI：
10.2337/diabetes.53.2.454
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发表时间：
2004-02-01
期刊：
影响因子：
7.7
通讯作者：
D'Amico, M
中科院分区：
文献类型：
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作者：
Marfella, R;Di Filippo, C;D'Amico, M
我们研究了诱导型一氧化氮合酶（iNOS）在基因缺陷型（iNOS（-/-））小鼠和野生型（iNOS（+/+））小鼠缺血性心肌损伤和血管生成过程中的作用，有和没有链脲佐菌素诱导（70 mg/kg静脉注射）糖尿病。缺血25 min再灌注120 min后，iNOS（+/+）和iNOS（-/-）糖尿病小鼠（血糖22 mmol/l）的心肌梗死面积均大于其相应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）、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）组织水平均较高。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），与最高的组织硝基酪氨酸和促炎细胞因子水平以及细胞凋亡相关。iNOS在调节缺血/再灌注损伤防御反应中的有益作用似乎在糖尿病小鼠中被取消。糖尿病53：454-462，2004年。
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. Diabetes 53:454-462, 2004.