Microcircutation in burned wound and usefulness of microcirculation modulation

烧伤创面的微循环和微循环调节的作用

• 批准号: 08671383
• 负责人: SHINOZAWA Yotaro
• 金额: $ 1.41万
• 依托单位: Keio 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 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671383/
• 关键词: burn shock; microcirculation; nitric oxide synthase inhibitor; nitric oxide; inducible nitric oxide synthase; constitutive nitric oxide synthase; endotoxin; nafamostat mesilate; エンドトキセミア; 蛋白分解酵素阻害薬; 一酸化窒素合成酵素阻害薬; 熱傷; 熱傷創; 創傷治癒; カテコラミン; ハイドロ

1. The effects of microcirculation in a third degree burned wound in the early phase of burn on the integrity was studied by evaluating insensible water loss (ISWL) in 30% TBSA burned SD rat. The effects of cNOS inhibitor (N^G-nitro-L-arginine 10 mg/kg) and iNOS (aminoguanidine 100 mg/kg) on urinary NOx (=N02+N03) excretion and on ISWL were also examined. Urinary NOx was considered to be excreted dominantly by iNOS and iNOS inhibitor seemed to be beneficial to maintain the microcirculation in burned wound.2. To search a clinically available iNOS inhibitor, sepsis rat model induced by repeatedly (five times) injected endotoxin (5-10 mg/kg) for 100 minutes was used. FUT-175 (clinically used as a protease iinhibitor) was examined as to protect iNOS dependent organ (liver, lung and stomach) injuries. Endotoxemia increased plasma NOx levels from 19.4+/-2.1 micro MIL of control levels up to 36.0+/-4.1, and decreased down to 26.5+1-7.4 by FUT-175 (1-2 mg/kg x2) administration. cNOS in liver and lung increased in endotoxemia, and iNOS increased in all examined organs by injection of endotoxin. FUT-175 administration decreased the increased iNOS activities to control levels.3. iNOS seemed to be dominant both in the early phase and in septic phase of burn, and NO modulation by FUT-175 is considered useful for maintain circulation and protection organ function in burned patients.

1.通过评估30%TBSA烧伤SD大鼠的不感水丢失(ISWL)，研究烧伤早期微循环对创面完整性的影响。还检查了cNOS抑制剂（N^G-硝基-L-精氨酸10mg/kg）和iNOS（氨基胍100mg/kg）对尿NOx（=N02+N03）排泄和ISWL的影响。尿NOx被认为主要通过iNOS排泄，iNOS抑制剂似乎有利于维持烧伤创面的微循环。2．为了寻找临床可用的iNOS抑制剂，采用反复（5次）注射内毒素（5-10mg/kg）100分钟诱导脓毒症大鼠模型。 FUT-175（临床上用作蛋白酶抑制剂）经检查可保护 iNOS 依赖性器官（肝、肺和胃）损伤。内毒素血症使血浆 NOx 水平从对照水平的 19.4+/-2.1 microMIL 增加至 36.0+/-4.1，并通过 FUT-175（1-2 mg/kg x2）给药降低至 26.5+1-7.4。内毒素血症时肝脏和肺中的cNOS增加，注射内毒素后所有检查器官中的iNOS增加。 FUT-175给药将增加的iNOS活性降低至控制水平。3． iNOS 似乎在烧伤的早期阶段和脓毒症阶段都占主导地位，FUT-175 对 NO 的调节被认为有助于维持烧伤患者的循环和保护器官功能。