Fouke J M, Wolin A D, McFadden E R
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH.
Prostaglandins. 1991 Oct;42(4):343-53. doi: 10.1016/0090-6980(91)90083-r.
To determine if acute exposure to ozone can cause changes in the production of cyclooxygenase metabolites of arachidonic acid (AA) in the lung which are associated with changes in lung mechanics, we exposed mongrel dogs to 0.5 ppm ozone for two hours. We measured pulmonary resistance (RL) and dynamic compliance (Cdyn) and obtained methacholine dose response curves and bronchoalveolar lavagate (BAL) before and after the exposures. We calculated the provocative dose of methacholine necessary to increase RL 50% (PD50) and analyzed the BAL for four cyclooxygenase metabolites of AA: a stable hydrolysis product of prostacyclin, 6-keto-prostaglandin F1 alpha (6-keto-PgF1 alpha); prostaglandin E2 (PgE2); a stable hydrolysis product of thromboxane A2, thromboxane B2 (TxB2); and prostaglandin F2 alpha (PgF2 alpha). Following ozone exposure, RL increased from 4.75 +/- 1.06 to 6.08 +/- 1.3 cm H2O/L/sec (SEM) (p less than 0.05), Cdyn decreased from 0.0348 +/- 0.0109 TO .0217 +/- .0101 L/cm H2O (p less than 0.05), and PD50 decreased from 4.32 +/- 2.41 to 0.81 +/- 0.49 mg/cc (p less than 0.05). The baseline metabolite levels were as follows: 6-keto PgF1 alpha: 96.1 +/- 28.8 pg/ml; PgE2: 395.8 +/- 67.1 pg/ml; TxB2: 48.5 +/- 11.1 pg/ml; PgF2 alpha: 101.5 +/- 22.6 pg/ml. Ozone had no effect on any of these prostanoids. These studies quantify the magnitude of cyclooxygenase products of AA metabolism in BAL from dog lungs and demonstrate that changes in their levels are not prerequisites for ozone-induced changes in lung mechanics or airway reactivity.
为了确定急性暴露于臭氧是否会导致肺部花生四烯酸（AA）的环氧化酶代谢产物生成发生变化，而这种变化与肺力学改变相关，我们将杂种狗暴露于0.5 ppm的臭氧中两小时。我们在暴露前后测量了肺阻力（RL）和动态顺应性（Cdyn），并获得了乙酰甲胆碱剂量反应曲线以及支气管肺泡灌洗液（BAL）。我们计算了使RL增加50%所需的乙酰甲胆碱激发剂量（PD50），并分析了BAL中AA的四种环氧化酶代谢产物：前列环素的稳定水解产物6-酮-前列腺素F1α（6-酮-PgF1α）；前列腺素E2（PgE2）；血栓素A2的稳定水解产物血栓素B2（TxB2）；以及前列腺素F2α（PgF2α）。臭氧暴露后，RL从4.75±1.06增加至6.08±1.3 cm H2O/L/秒（标准误）（p<0.05），Cdyn从0.0348±0.0109降至0.0217±0.0101 L/cm H2O（p<0.05），且PD50从4.32±2.41降至0.81±0.49 mg/cc（p<0.05）。基线代谢产物水平如下：6-酮-PgF1α：96.1±28.8 pg/ml；PgE2：395.8±67.1 pg/ml；TxB2：48.5±11.1 pg/ml；PgF2α：101.5±22.6 pg/ml。臭氧对这些前列腺素均无影响。这些研究量化了狗肺BAL中AA代谢的环氧化酶产物的量，并表明其水平变化并非臭氧诱导的肺力学或气道反应性变化的先决条件。
