Indomethacin inhibits the airway hyperresponsiveness but not the neutrophil influx induced by ozone in dogs.
Indomethacin inhibits the airway hyperresponsiveness but not the neutrophil influx induced by ozone in dogs.
复制标题
吲哚美辛可以抑制狗的气道高反应性，但不能抑制臭氧引起的中性粒细胞流入。
DOI：
10.1164/arrd.1984.130.2.220
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Nadel,JA
中科院分区：
文献类型：
--
作者：
O'Byrne,PM;Walters,EH;Aizawa,H;Fabbri,LM;Holtzman,MJ;Nadel,JA
为了确定花生四烯酸的氧化产物是否可能与臭氧暴露引起的气道高反应性有关，我们研究了狗体内的前列腺素合成酶抑制剂吲哚美辛是否可以抑制臭氧引起的高反应性。在两组实验中，通过乙酰胆碱气溶胶与肺阻力的剂量反应曲线来评估气道反应性：在一组实验中，5只狗没有接受吲哚美辛治疗，并且在臭氧暴露（3.0 ppm，2小时）之前和之后进行研究；在另一组中，在吲哚美辛治疗或臭氧暴露之前以及在臭氧暴露之前和之后的治疗期间（每 12 小时 1 毫克/千克，持续 4 天）对相同的狗进行了研究。每次，我们还测定了气道上皮活检中中性粒细胞的数量。当狗没有接受吲哚美辛治疗时，臭氧会导致对乙酰胆碱的反应性显着增加，并且气道上皮中的中性粒细胞数量显着增加。当狗给予吲哚美辛时，治疗期间的反应性与治疗前没有差异，但更重要的是，暴露于臭氧后反应性并没有显着增加。有趣的是，吲哚美辛治疗既不影响臭氧暴露前上皮中性粒细胞的基线数量，也不影响暴露后中性粒细胞数量的增加。结果表明，对吲哚美辛抑制敏感的花生四烯酸的氧化产物在臭氧诱导的高反应性中发挥作用，而不影响中性粒细胞的流入。
To determine whether oxygenation products of arachidonic acid may be involved in the airway hyperresponsiveness induced by ozone exposure, we studied whether ozone-induced hyperresponsiveness could be inhibited by the prostaglandin synthetase inhibitor, indomethacin, in dogs. Airway responsiveness was assessed with dose-response curves of acetylcholine aerosol versus pulmonary resistance in 2 sets of experiments: in one set, 5 dogs were given no indomethacin treatment and were studied both before and after ozone exposure (3.0 ppm, 2 h); in another set, the same dogs were studied before indomethacin treatment or ozone exposure and then during treatment (1 mg/kg every 12 h for 4 days) both before and after ozone exposure. On each occasion, we also determined the number of neutrophils in biopsies of the airway epithelium. When the dogs were not treated with indomethacin, ozone caused a marked increase in responsiveness to acetylcholine and a marked increase in the number of neutrophils in the airway epithelium. When the dogs were given indomethacin, responsiveness was no different during treatment than before treatment, but more importantly, responsiveness did not increase significantly after they were exposed to ozone. Interestingly, indomethacin treatment did not affect either the baseline number of epithelial neutrophils before ozone exposure or the increase in the number of neutrophils after exposure. The results suggest that oxygenation products of arachidonic acid that are sensitive to inhibition by indomethacin play a role in ozone-induced hyperresponsiveness without affecting the influx Of neutrophils.