Carey P D, Byrne K, Jenkins J K, Sielaff T D, Walsh C J, Fowler A A, Sugerman H J
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J Surg Res. 1990 Sep;49(3):262-70. doi: 10.1016/0022-4804(90)90131-k.
Hypochlorous acid (HOCl), a neutrophil-generated oxidant, has been implicated in tissue destruction in sepsis-induced acute lung injury (ALI). Ibuprofen, a cyclooxygenase inhibitor, successfully attenuates many of the physiological derangements in ALI. The aim of this study was to examine the role of PMN hypochlorous acid in sepsis-induced ALI and evaluate the effect of ibuprofen therapy. Neutrophils from three groups of young (15-25 kg), anesthetized swine were studied: controls (C, n = 7) received 0.9% NaCl, septic animals (Ps, n = 8) received live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min, and ibuprofen-treated animals (Ps + I, n = 6) received Ps plus ibuprofen 12.5 mg/kg administered at 0 and 120 min. Neutrophils were isolated from peripheral blood at 0, 60, and 300 min and the rate and total production of HOCl were assessed on the basis of the ability of the amino acid taurine to trap HOCl.
Septic (Ps) PMNs produce 32% more HOCl, P less than 0.01, at 300 min than at baseline which was associated with a marked increase in both extravascular lung water (6.44 +/- 0.8 ml/kg, t = 0 vs 16.03 +/- 2.6 ml/kg, t = 300, P less than 0.01) and bronchoalveolar protein content (115 +/- 13 micrograms/ml, t = 0 vs 633 +/- 104 micrograms/ml, t = 300, P less than 0.01). Ibuprofen significantly attenuated (P less than 0.05) HOCl production when compared to Ps, in conjunction with significantly (P less than 0.05) reduced levels of extravascular lung water and bronchoalveolar lavage protein.
次氯酸（HOCl）是一种由中性粒细胞产生的氧化剂，在脓毒症诱导的急性肺损伤（ALI）的组织破坏中起作用。布洛芬是一种环氧化酶抑制剂，可成功减轻ALI中的许多生理紊乱。本研究的目的是研究中性粒细胞次氯酸在脓毒症诱导的ALI中的作用，并评估布洛芬治疗的效果。研究了三组年轻（15 - 25千克）麻醉猪的中性粒细胞：对照组（C，n = 7）接受0.9%氯化钠，脓毒症动物（Ps，n = 8）接受活的铜绿假单胞菌（5×10⁸CFU/ml，以0.3 ml/20 kg/min的速度）60分钟，布洛芬治疗组动物（Ps + I，n = 6）接受Ps加布洛芬12.5 mg/kg，分别在0分钟和120分钟给药。在0、60和300分钟从外周血中分离中性粒细胞，并根据氨基酸牛磺酸捕获HOCl的能力评估HOCl的产生速率和总量。
脓毒症（Ps）组中性粒细胞在300分钟时产生的HOCl比基线时多32%，P < 0.01，这与血管外肺水（6.44 ± 0.8 ml/kg，t = 0时与16.03 ± 2.6 ml/kg，t = 300时，P < 0.01）和支气管肺泡蛋白含量（115 ± 13 μg/ml，t = 0时与633 ± 104 μg/ml，t = 300时，P < 0.01）的显著增加相关。与Ps组相比，布洛芬显著减弱（P < 0.05）HOCl的产生，同时显著（P < 0.05）降低血管外肺水和支气管肺泡灌洗蛋白的水平。
