The role CO radicals in the pathogenesis of shock and organ dysfunction

CO自由基在休克和器官功能障碍发病机制中的作用

• 批准号: 12671508
• 负责人: OGAWA Ryo
• 金额: $ 2.18万
• 依托单位: NIPPON MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671508/
• 关键词: CARBON MONOOXIDE RADICALS; SHOCK; MULTIPLE ORGAN DYSFUNCTION; ENDOTOXIN; CECAL LIGATION; NO・; CO・; L-CANAVANINE; ZINC PROTOPORPHYLLINE; Heme-oxygenase; Shock; organ tailure; 臓器不全; 炭素ラジカル; 一酸化炭素

In the present study, the role of carbon monoxide radicals (CO ・) in the pathogenesis of circulatory depression and multiple organ dysfunction was investigated. Wister strain rats with 300g of body weight were anesthetized with 65 mg/kg of pentobarbital sodium. The trachea was intubated to facilitate controlled respiration. The animals were induced into shock and multiple organ dysfunction by the intra-peritoneal injection of LPS (10mg/kg) or by the ligation-perforation of cecum. The blood pressures were monitored and venous blood was taken to analyze concentrations of nitrosyl hemoglobin (NO-Hb) and carboxyhemoglobin (CO-Hb). The ESR technique was applied to determine NO-Hb according to Sakamoto. The CO-Hb was measure using blood gas analyzer (Radiometer Co Ltd. Type ABL 625).The animals fell into shock within 6 hours in LPS injected group and within 12 hours in caecal ligation group. The pretreatment of 20 mg/kg of L-canabanine, an inhibitor of iNOS, maintained high values in blood pressure than sham-operated controls. The administration of zinc protoporphylline gave forth a good result in circulatory function in shock model. The blood levels of NO-Hb and/or CO-Hb in two shock models revealed a lowered value in comparison with sham operated controls. We also observed a declined presentation of messenger RNA of HO-1 in the hepatic cells with two types of shock.

本研究探讨了一氧化碳自由基（CO·）在循环抑制和多器官功能障碍发病机制中的作用。用戊巴比妥钠65 mg/kg麻醉体重300g的Wister品系大鼠。气管插管便于控制呼吸。腹腔注射LPS （10mg/kg）或结扎穿孔盲肠诱导休克和多脏器功能障碍。监测血压，取静脉血分析亚硝基血红蛋白（NO-Hb）和羧化血红蛋白（CO-Hb）浓度。根据Sakamoto，采用ESR技术测定NO-Hb。Co - hb采用血气分析仪（Radiometer Co . Ltd.）测定。abl625型)。LPS注射组在6 h内休克，盲肠结扎组在12 h内休克。预处理20 mg/kg的l -大麻碱（一种iNOS抑制剂）比假手术对照组保持较高的血压值。原茶碱锌对休克模型的循环功能有良好的影响。与假手术对照组相比，两种休克模型的血液NO-Hb和/或CO-Hb水平显示较低。我们还观察到HO-1信使RNA在两种休克类型的肝细胞中的表达下降。

项目成果

Ogawa R: "Can anti-prteases prevent shock"Progress in Medicine. 196(1). 77-80 (2001)

小川 R：“抗蛋白酶可以预防休克”医学进展。

Ogawa R: "Shock in "Twxtbook of Intensive Care Medicine""Shujunsha Publishing Co Ltd. 349-364

小川R：《《重症监护医学Twxtbook》中的休克》蜀军社出版社349-364

Kishikawa H, Ogawa R, et al.: "Nitric oxide suppresses hepatocye apoptosis induced By free radicals"Biomed Res. 22巻2号. 83-89 (2001)

Kishikawa H，Okawa R，等人：“一氧化氮抑制自由基诱导的肝细胞凋亡”Biomed Res.22，No.2.83-89(2001)

Ogawa R: "The concept of "septic shock"-A recent development"Pdiatrics of Japan. 41(12). 2139-2145 (2001)

小川 R：““感染性休克”的概念 - 最近的发展”日本儿科。

Kishikawa H, Ogawa R, et al.: "Nitric oxide suppresses hepatocyte apoptosis induced By free radicals"Biomed Res. 22巻2号. 83-89 (2001)

Kishikawa H，Okawa R，等人：“一氧化氮抑制自由基诱导的肝细胞凋亡”Biomed Res.22，No.2.83-89(2001)