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.以SD大鼠30%TBSA烧伤模型为研究对象，通过测定无感觉水丢失量（ISWL），探讨了Ⅲ度烧伤早期微循环对创面完整性的影响。还检查了cNOS抑制剂（N4 G-硝基-L-精氨酸10 mg/kg）和iNOS（氨基胍100 mg/kg）对尿NOx（= NO2 + NO3）排泄和对ISWL的影响。尿中NOx主要由iNOS排出，iNOS抑制剂可能有助于维持烧伤创面微循环.为了寻找临床上可用的iNOS抑制剂，使用了通过重复（5次）注射内毒素（5-10 mg/kg）100分钟诱导的脓毒症大鼠模型。研究FUT-175（临床上用作蛋白酶抑制剂）对iNOS依赖性器官（肝、肺和胃）损伤的保护作用。内毒素血症使血浆NOx水平从对照水平的19.4+/-2.1微MIL增加至36.0+/-4.1，并且通过FUT-175（1-2 mg/kg x2）施用降低至26.5 ± 1-7.4。内毒素血症时肝、肺cNOS均升高，内毒素注射后各脏器iNOS均升高。FUT-175给药使增加的iNOS活性降低至对照水平.在烧伤早期和脓毒症期，iNOS均占主导地位，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。