目的 探讨氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤（acute lung injury, ALI）的影响。方法 成年雄性SD大鼠100只，体重280 g ~ 320 g，采用计算机简单随机分组法随机分为5组（每组20只）：对照组（C组）、内毒素组（L组）、氯胺酮组（K组）、乌斯他丁组(U组)、氯胺酮复合乌斯他丁组(K+U组)。除C组外，其余大鼠腹腔注射0.03 %脂多糖（lipopolysaccharide, LPS）1 mg/kg，注射后16 h时，由尾静脉再次注射0.l % LPS 1.5 mg/kg，建立大鼠ALI 模型。U组、K+U组分别在第2次注射LPS后经尾静脉注射乌司他丁 50 000 U/kg，注射乌司他丁后即刻，K 组、K+U 组经尾静脉以微量泵持续输注氯胺酮 10 ㎎•㎏-1•h-1，其余组注射等容量生理盐水。于第2次注射 LPS 后1、2、3、4 h (T1~4)时，各组取5只大鼠，抽取腹主动脉血样0.5 ml，测定氧分压（PaO2），抽取下腔静脉血样2 ml，测定血清肿瘤坏死因子（tumor necrosis factor，TNF）-α和白介素（interleukin，IL）-6浓度；放血处死大鼠，取右肺上叶组织，光镜下观察肺组织病理学结果，进行肺组织病理半定量评分及测定核因子（nuclear factor-κB, NF-κB）抑制蛋白α (inhibitor of nuclear factor-κBα, IκBα)表达；取右肺中叶组织100 mg测定肺组织NF-κB活性；取右肺下叶组织，计算肺湿干重比（W/D）。结果 与C组比较，L组、K组、U组和K+U组PaO2降低，血清TNF-α、IL-6浓度和肺组织NF-κB活性升高，IκBα表达降低， W/D升高(P<0.01)；与L组比较，K组、U组和K+U组PaO2升高，血清TNF-α、IL-6浓度和肺组织NF-κB活性降低，IκBα表达升高，W/D降低，肺组织病理评分降低 (P<0.05或0.01)；与K组和U组比较，K+U组各时点PaO2升高，血清TNF-α、IL-6浓度和肺组织NF-κB活性（2.49±0.23）降低，IκBα表达（35.1±3.4）升高，W/D（4.91±0.16）降低，肺组织病理评分（7.8±0.8）降低(P<0.05或0.01) 。结论 氯胺酮复合乌司他丁可减轻大鼠ALI，较两者单独应用效果显著。
Objective To investigate the effects of ketamine combined with ulinastatin against endotoxin-induced acute lung injury (ALI) in rats. Methods One hundred healthy male SD rats, weight 208 g-320 g, were randomly divided into 5 groups equally: groupⅠnormal control (C); groupⅡ endotoxin (L); group Ⅲ ketamine (K); group Ⅳ ulinastatin (U) and groupⅤ(K+U). The animals received 2 doses of LPS (intraperitoneal LPS 1 mg/kg and iv LPS 1.5 mg/kg) at 16 h interval in groupⅡtogroupⅤ. The animals received ulinastatin 50 000 U/kg iv after second dose of LPS in group U and K+U. Ketamine was infused iv at 10 mg/kg/h in group K and K+U. Five animals in each group were killed by exsanguination at 1, 2, 3 and 4 h after second LPS administration. W/D lung weight ratio, blood gases, serum TNF-αand IL-6 concentrations and NF-КB activity and IκBα protein expression in the lung tissue were determined. Results LPS administration significantly increased serum TNF-αand IL-6 concentration and NF-κB activity in the lung tissue and decreased IκBα protein expression in groupⅡas compared with control group. The LPS-induced changes were attenuated by K/U/K+U in group Ⅲ, Ⅳ andⅤ. Compared with group K or group U, serum TNF-αand IL-6 concentration and NF-κB activity （2.49±0.23）in the lung tissue decreased and IκBα protein expression （35.1±3.4）increased significantly in group K+U. The protective effects of ketamine and ulinastatin against LPS-induced injury were synergistic. Conclusions Ketamine and ulinastatin have protective effects against LPS induced acute lung injury by inhibiting NF-КB activity, neutrophil activation and inflammatory responses, and are synergistic.
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