Experimental study of traumatic DIC -NO production in tissue and histopathology following hemorragic invasion in the rat-

大鼠出血性侵袭后组织和组织病理学中创伤性 DIC -NO 产生的实验研究

• 批准号: 10671108
• 负责人: SUGA Hiroyasu
• 金额: $ 2.05万
• 依托单位: Fukui Medical 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-10671108/
• 关键词: hemorrhagic invasion; endotoxin adminstration; NO production; NO synthase inhibitors; histopathology; coagulation-fibrinolytic system; cytokine; traumatic DIC; 出血性ショック; エンドトキシン; NO; cNOS; iNOS; NOS阻害剤

Previously, in order to study the pathogenesis of traumatic DIC, we investigated and confirmed the onset of DIC following hemorrhagic invasion in the rat, and at that time we noticed a rapid increase in nitric oxide (NO) in the tissue in the early stage after the invasion. It was suggested that the increase in NO production would serve as an indication for diagnosis of traumatic DIC. In this study, we investigated the time course and mechanism of NO production in the tissue and its histopathology following hemorragic invasion in the rat, in comparsion with the rat following endotoxin administration. Then we investigated therapeutic effects of NO synthase (NOS) inhibitors for these morbid states.In the fiscal year 1998, the time course of NO production in the tissue following hemorrhagic invasion (bleeding of 30% of predetermined total blood volume) in the rat was recorded with an NO-selective electrode(φ200μm, Intermedical Co.) set in the kidney tissue, comparing with that rat followin … More g endotoxin administration (LPS, E, coli, 10mg/kg iv). In the hemorrhagic invasion, increase in NO production in the early stage was observed and it was suggested strongly to be due to constitutive NOS (cNOS) by the investigation with NOS inhibitors. On the contrary, in the endotoxin administration NO production was not observed at all in the early stage, but it begun to increase gradually 2〜3hr after the administration and reached a peak after 4〜6hr, and it was suggested strongly to be due to inducible NOS (iNOS). We could detect a characteristic ESR signal of NO in the sample solution of the kidney tissue following both the invasions.In the fiscal year 1999, therapeutic effects of NOS inhibitors and other drugs for these morbid states were investigated. NOS inhibitors have been tried to treat for various types of circulatory shock. In this experiment NOS inhibitors reduced partly the changes in the coagulation-fibrinolytic system and plasma cytokine levels induced by the invasions, but did not ameliorate significantly histopathological changes. On the other hand, antithrombin III ameliorated changes in coagulation-fibrinolytic system and plasma cytokine levels, and also histopathological changes, too. Theraputic effects of NOS inhibitors for these morbid states should be further investigated in detail on types, dosages, time of treatment of NOS inhibitors, considering two sided roles of NO effect. Less

此前，为了研究创伤性DIC的发病机制，我们对大鼠出血性侵袭后DIC的发病进行了调查并证实，当时我们注意到术后早期组织中一氧化氮（NO）快速升高。有人认为，NO 产生的增加可以作为诊断创伤性 DIC 的指标。在这项研究中，我们研究了出血性侵袭后组织中 NO 产生的时间过程和机制及其组织病理学。然后我们研究了 NO 合酶 (NOS) 抑制剂对这些病态的治疗效果。在 1998 财年，在随后的组织组织侵袭（出血）中 NO 产生的时间过程。用设置在肾组织中的NO选择性电极（φ200μm，Intermedical Co.）记录大鼠体内预定总血容量的30％，并与大鼠进行比较随后给予g内毒素（LPS、E、大肠杆菌，10mg/kg iv）。在出血性侵袭中，观察到早期NO产生增加，调查表明这是由于组成型NOS（cNOS）所致。相反，内毒素给药早期根本观察不到NO产生，但在给药后2~3小时开始逐渐增加，并在给药后达到峰值。 4-6小时，强烈提示是由于诱导型NOS（iNOS）所致。在两次侵袭后，我们可以在肾组织样品溶液中检测到NO的特征ESR信号。在1999财年，治疗效果。 NOS 抑制剂和其他治疗这些病态的药物已被尝试用于治疗各种类型的循环休克。在该实验中，NOS 抑制剂部分地减少了凝血-纤溶的变化。抗凝血酶 III 改善了凝血纤溶系统和血浆细胞因子水平的变化，但并没有显着改善组织病理学变化，也改善了 NOS 抑制剂的治疗效果。这些病态应进一步详细研究NOS抑制剂的类型、剂量、治疗时间，并考虑NO效应的两个方面作用。

项目成果

Nakagawa T. Suga,h.et al: "Experimental study on the onset of traumatic DIC : changes in the coagulofibrinolytic system, blood cytokine. levels and histopathological findings following hemorrhage in rats"J Tokyo Wom Med Univ. 69. 396-403 (1999)

Nakakawa T. Suga,h.et al：“创伤性 DIC 发病的实验研究：大鼠出血后凝血纤维蛋白溶解系统、血液细胞因子水平和组织病理学结果的变化”J Tokyo Wom Med Univ。

Suga,H.et al: "Nitric oxide production and occurrence of disseminated intravascular coagulation in the bleeding invasion rat"The Biology of Nitric oxide. Part 6. 179 (1997)

Suga，H.等人：“出血侵袭大鼠中一氧化氮的产生和弥散性血管内凝血的发生”一氧化氮生物学。

Suga,H.et al: "Experimental study on the pathogenesis of traumatic DIC : Changes in plasma cytokine Level and coagulofibrinolytic system in the hemorrhage"Proceedings of the 4th International Congress on the Immune Consequences of trauma, shock and sepsis

Suga,H.等：“创伤性DIC发病机制的实验研究：出血中血浆细胞因子水平和凝血纤溶系统的变化”第四届国际创伤、休克和脓毒症免疫后果大会论文集

須賀弘泰: "ラットの腹腔内蔵器に於ける出血性DICと敗血症性DIC時のNO産生と病理組織学的変化" 第31回腹部救急学会・千葉・98.9.3.

Hiroyasu Suga：“大鼠腹部内脏出血性 DIC 和脓毒性 DIC 期间 NO 的产生和组织病理学变化”第 31 届腹部紧急会议，千叶，98.9.3。

須賀弘泰ほか: "敗血症性DICラットに対するNOS阻害剤の治療効果"日本ショック学会雑誌. 14(2). 19-23 (1999)

Hiroyasu Suga 等人：“NOS 抑制剂对脓毒症 DIC 大鼠的治疗效果”，日本休克学会杂志 14(2) (1999)。