Carey P D, Jenkins J K, Byrne K, Walsh C J, Fowler A A, Sugerman H J
Department of Surgery, Medical College of Virginia, Richmond 23229.
Surgery. 1992 Jul;112(1):45-55.
Cyclooxygenase inhibition has been proposed as treatment for sepsis-induced acute lung injury. However, the mechanism of protection offered by the cyclooxygenase inhibitor ibuprofen is not well understood. To elucidate this mechanism, the effects of ibuprofen on the neutrophil respiratory burst and alveolar-capillary membrane leak were studied. Anesthetized swine (15 to 25 kg) were intubated and mechanically ventilated (fraction of inspired oxygen, 0.5). Control animals (n = 5) received a sham infusion of 0.9% NaCl, animals with sepsis (n = 10) received a 1-hour infusion of live Pseudomonas aeruginosa (5 x 10(8) colony-forming units/ml at 0.3 ml/20 kg/hr), and treated animals (ibuprofen-treated control animals [n = 4] or ibuprofen-treated animals with sepsis [n = 9]) received ibuprofen (12.5 mg/kg at 0 and 120 minutes). All animals were studied for 300 minutes. Neutrophils were isolated at 0, 60, and 300 minutes. Neutrophil superoxide anion production (O2-) was assessed in a kinetic fashion (in nanomoles per minute) by superoxide dismutase-inhibitable cytochrome C reduction (phorbol myristate acetate stimulation). Bronchoalveolar lavage protein estimation (0 and 300 minutes) and extravascular lung water (double indicator dilution) were performed to assess alveolar-capillary membrane leak. Ibuprofen significantly attenuated sepsis-enhanced maximum neutrophil generation of O2- (6.0 +/- 0.5 nmol/min for animals with sepsis, 300 minutes, vs 4.1 +/- 0.5 nmol/min for ibuprofen-treated animals, with sepsis, 300 minutes; p less than 0.05), indicating an in vivo down-regulatory effect on neutrophil oxidant generation. Ibuprofen also prevented increased airspace bronchoalveolar lavage protein and extravascular lung water accumulation, suggesting a protective effect on the alveolar-capillary membrane. This protective effect of ibuprofen in acute lung injury may be through a decreased neutrophil respiratory burst.
环氧化酶抑制已被提议用于治疗脓毒症诱导的急性肺损伤。然而，环氧化酶抑制剂布洛芬所提供的保护机制尚未完全明确。为阐明此机制，研究了布洛芬对中性粒细胞呼吸爆发及肺泡-毛细血管膜渗漏的影响。将麻醉的猪（15至25千克）插管并进行机械通气（吸入氧分数为0.5）。对照组动物（n = 5）接受0.9%氯化钠的假输注，脓毒症动物（n = 10）接受1小时的活铜绿假单胞菌输注（5×10⁸菌落形成单位/毫升，以0.3毫升/20千克/小时的速度），而治疗组动物（布洛芬治疗的对照组动物[n = 4]或布洛芬治疗的脓毒症动物[n = 9]）接受布洛芬（在0分钟和120分钟时各12.5毫克/千克）。所有动物均研究300分钟。在0、60和300分钟时分离中性粒细胞。通过超氧化物歧化酶抑制的细胞色素C还原（佛波酯肉豆蔻酸酯刺激）以动力学方式（每分钟纳摩尔数）评估中性粒细胞超氧阴离子生成（O₂⁻）。进行支气管肺泡灌洗蛋白测定（0和300分钟）和血管外肺水（双指示剂稀释法）以评估肺泡-毛细血管膜渗漏。布洛芬显著减弱了脓毒症增强的中性粒细胞O₂⁻最大生成量（脓毒症动物在300分钟时为6.0±0.5纳摩尔/分钟，而布洛芬治疗的脓毒症动物在300分钟时为4.1±0.5纳摩尔/分钟；p＜0.05），表明对中性粒细胞氧化剂生成有体内下调作用。布洛芬还防止了肺泡支气管灌洗蛋白和血管外肺水积聚的增加，提示对肺泡-毛细血管膜有保护作用。布洛芬在急性肺损伤中的这种保护作用可能是通过减少中性粒细胞呼吸爆发实现的。
