Carey P D, Leeper-Woodford S K, Walsh C J, Byrne K, Fowler A A, Sugerman H J
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23229.
J Trauma. 1991 Jun;31(6):733-40; discussion 740-1. doi: 10.1097/00005373-199106000-00002.
Ibuprofen pretreatment attenuates the enhanced neutrophil (PMN) respiratory burst and reduces increased plasma tumor necrosis factor (TNF) activity in porcine sepsis-induced acute lung injury (ALI). These septic responses have been linked to increased alveolar-capillary membrane (ACM) permeability. This study was designed to establish whether delayed ibuprofen treatment would have the same effect and to examine the relationship between PMN oxidant generation and TNF. Three groups of anesthetized, ventilated pigs (15-25 kg) were used. Group Ps received Pseudomonas aeruginosa (5 x 10(8) CFU/mL at 0.3 mL/20 kg/min) for one hour IV; The control group (Con) received 0.9% NaCl. Group D-Ibu received ibuprofen 12.5 mg/kg as a delayed bolus at 30 minutes and again at 120 minutes after Ps. Protein (BAL-P, microgram/mL) in harvested bronchoalveolar lavage fluid and extravascular lung water (EVLW, mL/kg) were used to estimate the integrity of the ACM. Superoxide anion (O2-) generation (ferricytochrome c reduction) from circulating PMNs and plasma TNF activity (L929 fibroblast bioassay) were measured. The EVLW increased significantly (p less than 0.05), as did BAL-P (p less than 0.01), in the P. aeruginosa-treated animals at 300 minutes. These increases were abolished in Group D-Ibu: EVLW, 6.6 +/- 1.0 baseline vs. 14.6 +/- 2.6 Ps 300 vs. 6.8 +/- 0.9 D-Ibu 300; BAL-P, 175 +/- 28 baseline vs. 984 +/- 186 Ps 300 vs. 284 +/- 42.8 D-Ibu 300. Both enhanced PMN oxidant activity and increased plasma TNF activity were significantly attenuated by delayed ibuprofen treatment. These data support the efficacy of the nonsteroidal anti-inflammatory drug, ibuprofen, when used after the onset of a septic stimulus.
布洛芬预处理可减轻猪败血症诱导的急性肺损伤（ALI）中增强的中性粒细胞（PMN）呼吸爆发，并降低血浆肿瘤坏死因子（TNF）活性的升高。这些败血症反应与肺泡-毛细血管膜（ACM）通透性增加有关。本研究旨在确定延迟给予布洛芬治疗是否会产生相同的效果，并研究PMN氧化剂生成与TNF之间的关系。使用了三组麻醉通气的猪（15-25千克）。Ps组静脉注射铜绿假单胞菌（5×10⁸CFU/mL，0.3 mL/20 kg/min）1小时；对照组（Con）接受0.9%氯化钠。D-Ibu组在Ps组注射后30分钟和120分钟分别给予12.5 mg/kg布洛芬作为延迟推注。采集的支气管肺泡灌洗液中的蛋白质（BAL-P，微克/毫升）和血管外肺水（EVLW，毫升/千克）用于评估ACM的完整性。测量循环PMN产生的超氧阴离子（O₂⁻）（高铁细胞色素c还原）和血浆TNF活性（L929成纤维细胞生物测定）。在300分钟时，铜绿假单胞菌治疗的动物中，EVLW显著增加（p<0.05），BAL-P也显著增加（p<0.01）。D-Ibu组消除了这些增加：EVLW，基线6.6±1.0 vs Ps组300分钟时14.6±2.6 vs D-Ibu组300分钟时6.8±0.9；BAL-P，基线175±28 vs Ps组300分钟时984±186 vs D-Ibu组300分钟时284±42.8。延迟给予布洛芬治疗可显著减轻PMN氧化剂活性增强和血浆TNF活性增加。这些数据支持非甾体抗炎药布洛芬在败血症刺激发作后使用的有效性。
