Nitric oxide and superoxide in ishcemia/reperfusion injury

方法：实验1）雄性Wistar大鼠（250-350 g/只），肠缺血30 min，再灌注60 min，取小肠，用放射免疫法测定肠组织中NO的含量。缺血前10 min静脉注射NO合成酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，10 mg/kg）、NO生成底物L-精氨酸（L-Arg，300 mg/kg）或生理盐水（5 ml/kg）。术中监测动脉血压、门静脉血流量、肝组织和肾组织血流量作为血流动力学参数。在手术结束时研究血浆还原型谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG），以评价氧化应激。实验2）对雄性Wistar大鼠（250-350克）的部分肝叶进行缺血/再灌注。L-精氨酸（600 mg/kg/h）、L-NAME（20 mg/kg/h）和生理盐水（5 ml/kg/h）组分别于24 h、30 h、40 h、50 h、60 h、70 h、100 h ...更多信息 在缺血前10分钟静脉内微量给药。在手术过程中监测I/R非I/R叶中的肝微血管血流作为血流动力学参数。研究I/R和非I/R叶中的GSH和GSSG，以评估手术结束时的氧化应激。I/R叶和非I/R叶的损害进行了检查microscopic.RESULTS.实验1和2表明，抑制NO的产生恶化器官血流加剧组织破坏IRI与氧化应激增加。L-NAME治疗恶化微血管循环，增加粘膜损伤。此外，抑制NO的产生减轻了急性肠缺血/再灌注模型和部分肝缺血/再灌注模型中的氧化应激。在实验1中，L-NAME治疗的大鼠表现出显着的粘膜坏死，表面上皮破坏，固有层充血和出血和粘膜下坏死，而L-Arg治疗的大鼠末端回肠样品的组织病理学分级低。L-精氨酸治疗对肠和部分肝缺血/再灌注损伤的保护作用可能与其通过刺激内源性NO产生来防止微血管收缩的能力有关。少

PURPOSE.To evaluate the role of nitric oxide in ischemia/reperfusion injury.METHODS.Experiment 1) Male Wistar rats (250-350 gin) were underwent intestinal ischemia for 30 minutes and reperfusion for 60 minutes. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), the substrate for NO generation, L-arginine (L-Arg, 300 mg/kg) or saline (5 ml/kg) were administered intravenously 10 minutes before ischemia. Arterial blood pressure, portal blood flow, hepatic- and intestinal-tissue blood flow were monitored as hemodynamic parameters during the procedure. Plasma reduced glutathione (GSH) and oxidized glutathione (GSSG) were investigated to evaluate oxidant stress at the end of the procedure. The damage of the resected specimen of the ileum was examined microscopically.Experiment 2) Ischmeia/reperfusion of the partial lobe of the liver in Male Wistar rats (250-350 gm) were perfumed. The L-NAME (20 mg/kg/h), the L-arginine (600 mg/kg/h) or saline (5 ml/kg/h) were con … More tineously administered intravenously 10 minutes before ischemia. Hepatic microvascular blood flow in the I/R non-I/R lobes were monitored as hemodynamic parameters during the procedure. GSH and GSSG in the I/R and non-I/R lobes were investigated to evaluate oxidant stress at the end of the procedure. The damage of the I/R lobe and non-I/R lobes was examined microscopically.RESULTS.The experiment 1 and 2 reveals that inhibition of NO production deteriorated organ blood flow exacerbated tissue destruction in IRI with increased oxidant stress. L-NAME treatment deteriorates microvascular circulation, increases mucosal damage. Moreover, inhibition of NO production aggravates oxidant stress in both acute intestinal ischemia/reperfusion model and partial hepatic ischemia/reperfusion model. In experiment 1, L-NAME-treated rats showed significant mucosal necrosis, surface epithelial disruption, lamina propria congestion and hemorrhage and submucosal necrosis, while L-Arg-treated rats had low histopathologic grading of terminal ileal samples. The protective effect of L-arginine treatment on intestinal and partial hepatic ischemia/reperfusion injury may be related its ability to prevent microvascular constriction by the stimulation of endogenous NO production. Less