Microcircutation in burned wound and usefulness of microcirculation modulation

1.以30%烧伤SD大鼠为模型，观察烧伤早期三度烧伤创面微循环对创面完整性的影响。同时观察一氧化氮合酶抑制剂(N、G-硝基-L-精氨酸10 mg/kg)和诱导型一氧化氮合酶(氨基胍100 mg/kg)对大鼠尿NOx(=N02+N03)排泄量和ISWL的影响。结论：1.烧伤后尿液中NOx主要由iNOS排泄，iNOS抑制剂似乎有利于维持创面微循环。为寻找临床可用的诱导型一氧化氮合酶(INOS)抑制剂，采用多次(5~10 mg/kg)注射内毒素(5~10 mg/kg)100min建立脓毒症大鼠模型。研究了临床使用的蛋白酶抑制剂FUT-175对iNOS依赖的器官(肝、肺和胃)损伤的保护作用。内毒素血症使血浆NOx水平从对照组的19.4+/-2.1微米升至36.0+/-4.1，经FUT-175(1-2 mg/kg x2)治疗后降至26.5+1-7.4。内毒素血症大鼠肝、肺组织cNOS表达增加，iNOS表达增加。给予FUT-175可减少iNOS活性的升高，从而达到控制水平。在烧伤早期和脓毒症阶段，iNOS似乎占主导地位，FUT-175对维持循环和保护器官功能没有作用。

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.