Nitric oxide and superoxide in ishcemia/reperfusion injury

一氧化氮和超氧化物在缺血/再灌注损伤中的作用

• 批准号: 08671400
• 负责人: YONEKURA Takeo
• 金额: $ 1.41万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671400/
• 关键词: Nitric oxide; superoxide; ischemia; reperfusion; organ injury; oxidant stress; microvascular circulation; glutathione

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

[方法]实验1)雄性Wistar大鼠(250-350GIN)造成肠缺血30min，再灌流60min。缺血前10min静脉注射NO合成底物N-硝基-L-精氨酸甲酯(L-NAME，10 mg/kg)、L精氨酸(L-Arg，300 mg/kg)或生理盐水(5ml/kg)。术中监测动脉血压、门静脉血流量、肝和肠组织血流量作为血流动力学参数。在手术结束时检测血浆还原型谷胱甘肽(GSH)和氧化谷胱甘肽(GSSG)以评估氧化应激。实验2)灌胃雄性Wistar大鼠(250~350克)部分肝叶缺血再灌流。L-NAME(20 mg/kg/h)、L-精氨酸(600 mg/kg/h)或生理盐水(5ml/kg/h)均为…。更多的是在缺血前10分钟静脉注射。术中监测肝脏I/R非I/R叶微血管血流作为血流动力学参数。检查I/R叶和非I/R叶的GSH和GSSG，以评估氧化应激。结果实验1和实验2显示，随着氧化应激的增加，抑制NO的产生恶化了器官血流，加剧了IRI的组织破坏。L的治疗恶化了微血管循环，增加了粘膜损伤。此外，在急性肠缺血/再灌流模型和部分肝缺血/再灌流模型中，抑制NO的产生均加重氧化应激。实验一，L组大鼠回肠黏膜明显坏死，表面上皮破裂，固有层充血出血，黏膜下坏死，L精氨酸组大鼠回肠末端组织病理分级较低。L-精氨酸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的产生而防止微血管收缩有关。较少

项目成果

米倉竹夫,窪田昭男: "新生児壊死性腸炎の病態-腸管阻血性病変とnitric oxide" 医学のあゆみ. 12. 863-864 (1998)

Takeo Yonekura、Akio Kubota：“新生儿坏死性小肠结肠炎的病理学 - 肠道缺血性病变和一氧化氮”医学史 12. 863-864 (1998)。

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Yonekura T、Kubota A、Oyanagi H：“自由基诱发的生理障碍和疾病。”

Yonekura T, Kubota A, Oyanagi H: "The role of nitric oxide in sepsic shock" Mediya Circle. 40. 45-51 (1995)

Yonekura T、Kubota A、Oyanagi H：“一氧化氮在脓毒症休克中的作用”Mediya Circle。

Yonekura T, Kubota A, Hoki M,et al: "Surgical intervention for a pancreatoblastoma associated with tumor thrombus in the portal vein." Medical Pediatr Oncology. 31. 359 (1998)

Yonekura T、Kubota A、Hoki M 等人：“与门静脉肿瘤血栓相关的胰母细胞瘤的手术干预。”

Yonekura T, Matsusue S, Walser M.: "Ketoisocaproate infusion improves survival from experimental sepsis by antioxidant mechanism." Circ Shock. 41. 213-220 (1993)

Yonekura T、Matsusue S、Walser M.：“酮异己酸输注通过抗氧化机制提高了实验性败血症的存活率。”