Mechanism of multiple organ failure caused by interaction of nitric oxide and oxidant stress

一氧化氮与氧化应激相互作用引起多器官衰竭的机制

• 批准号: 10671142
• 负责人: YONEKURA Takeo
• 金额: $ 2.05万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671142/
• 关键词: nitric oxide; oxidant stress; ischemia reperfusion injury; glutathione; sepsis; hyperendotoxemia; drug delivery system; オキシダンストレス; 虚血再灌流障害; poly(ADP-riboss)polymerase; benzamide; ATP; 酸素ラジカル; 虚血再灌流; 臓器障害; oxidant stress; 組織血流障害; 循環障害; グル

Research 1 : Interaction of nitric oxide (NO) and free radical is suspected the cause of multiple organ failure in ischemia reperfusion injury. In this research, we evaluated effect of nitric oxide on oxidant stress to estimate mechanism of cellular injury in ischemia reperfusion using partial hepatic ischemia-reperfusion model. Rats were subjected to ischemia and reperfusion in the lateral lobe of the liver. After continuous administration of NG-nitro-L-arginine methyl ester (L-NAME), L-arginine (L-Arg) or saline, we evaluated tissue blood flow and concentrations of oxidized and reduced glutathione in the I/R-lobe and the non-I/R-lobe in each group. Inhibition of NO production deteriorated tissue blood flow, hepatic injury and oxidant stress in both the I/R-lobe and the non-I/R-lobe. Administration of L-Arg had only transient increase of tissue blood flow in the I/R-lobe, moreover deteriorated hepatic injury and oxidant stress.Research 2 : Sepsis often causes multiple organ failure. To reveal the mechanism of septic organ failure, we developed a novel reproducible septic animal model applying drug delivery system (DDS). Rats implanted with DDS contained with lipopolysaccharide maintained high blood levels of endotoxin for 72 hours, and also exhibited septic condition.

研究1：一氧化氮(NO)与自由基的相互作用可能是脑缺血再灌注损伤中多器官衰竭的原因。本研究采用大鼠部分肝缺血再灌流模型，观察一氧化氮对氧化应激的影响，探讨缺血再灌注时细胞损伤的机制。建立大鼠肝外侧叶缺血再灌流模型。连续给予N-硝基-L-精氨酸甲酯(L-NAME)、L-精氨酸(L-Arg)或生理盐水后，测定各组I/R叶和非I/R叶组织血流量及氧化和还原谷胱甘肽浓度。抑制NO的产生恶化了I/R叶和非I/R叶的组织血流量、肝损伤和氧化应激。应用L-精氨酸后，I/R叶组织血流量仅一过性增加，肝损伤加重，氧化应激加重。研究二：脓毒症常导致多器官功能衰竭。为了揭示败血症器官衰竭的机制，我们应用药物释放系统(DDS)建立了一种新的可重复性的败血症动物模型。植入含有内毒素的DDS的大鼠在72小时内保持高水平的内毒素，并表现出脓毒症状态。

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 (1999)

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 (1999)。

Yonekura T,Kubota A 他: "Inhibition of nitric oxide production deteriorates intestinal ischemia reperfusion injury due to increased oxidant stress"Shock. (in press).

Yonekura T、Kubota A 等人：“由于氧化应激增加，抑制一氧化氮的产生会恶化肠道缺血再灌注损伤”（出版中）。

Yonekura T,Kubota A,: "Inhibition of nitric production deteriorates intestinal ischemia reperfusion injyury due to increased"Shock. (印刷中).

Yonekura T，Kubota A，：“抑制硝酸盐的产生会因增加休克而恶化肠道缺血再灌注损伤”（正在出版）。

米倉竹夫、窪田昭男: "新生児壊死性腸炎の病態-腸管虚血性病変とnitric oxide"医学のあゆみ. 186. 863 (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 186. 863 (1998)。

米倉武夫: "系統小児外科学 第7章 人工臓器 付)Nitric oxide第1版"永井書店(印刷中).

米仓武雄：《系统性小儿外科第 7 章人工器官）一氧化氮第 1 版》永井书店（目前正在印刷）。