Microcircutation in burned wound and usefulness of microcirculation modulation

1. 通过评价30% TBSA烧伤SD大鼠早期三度烧伤创面的不知觉失水（ISWL），研究烧伤早期微循环对创面完整性的影响。研究了nos抑制剂（N^ g -硝基- l -精氨酸10 mg/kg）和iNOS（氨基胍100 mg/kg）对尿NOx （=N02+N03）排泄和ISWL的影响。泌尿系统NOx主要通过iNOS排出，iNOS抑制剂有利于维持烧伤创面微循环。为寻找临床可用的iNOS抑制剂，采用5次多次注射内毒素（5 ~ 10 mg/kg）致脓毒症大鼠模型，持续100分钟。检测FUT-175（临床上用作蛋白酶i抑制剂）对iNOS依赖器官（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升高到36.0+/-4.1,FUT-175 （1-2 mg/kg x2）处理后降至26.5+1-7.4。内毒素血症组肝、肺的iNOS升高，注射内毒素组各脏器iNOS升高。FUT-175使升高的iNOS活性降低至控制水平。iNOS似乎在烧伤早期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。

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.