Chitano P, Di Stefano A, Finotto S, Zavattini G, Maestrelli P, Mapp C, Fabbri L M, Allegra L
Institute of Occupational Medicine, University of Padua, Italy.
Respiration. 1989;55 Suppl 1:74-8. doi: 10.1159/000195755.
To follow up previous observations that airway hyperresponsiveness induced by ozone is linked to airway inflammation and particularly to the release of arachidonic acid metabolites, we investigated the effect of ambroxol (a mucoactive and surfactant-stimulating drug that has recently been discovered to inhibit the release of arachidonic acid from cell membrane phospholipids) on airway hyperresponsiveness and bronchoalveolar neutrophilia induced by ozone in dogs. One group of 5 dogs was studied before treatment with nebulized saline and then after exposure to ozone (3 ppm, 1 h); another group of 6 dogs was studied before treatment with ambroxol (100 breaths of a 1% solution) and after exposure to ozone. On each occasion, we measured airway responsiveness to acetylcholine and counted the number of cells in bronchoalveolar lavage fluid. When the dogs were given the saline placebo, ozone induced a marked increase in airway responsiveness to acetylcholine and a marked influx of neutrophils in the airways. When the dogs were given ambroxol, ozone induced the same increase in the number of neutrophils in bronchoalveolar lavage, but did not increase the degree of airway responsiveness to acetylcholine. We conclude that ambroxol inhibits ozone-induced airway hyperresponsiveness in dogs, probably by inhibiting the formation and release of oxygenation products of arachidonic acid from neutrophils.
为了跟进之前的观察结果，即臭氧诱导的气道高反应性与气道炎症相关，尤其是与花生四烯酸代谢产物的释放有关，我们研究了氨溴索（一种黏液活性和刺激表面活性剂的药物，最近发现它能抑制细胞膜磷脂中花生四烯酸的释放）对臭氧诱导的犬气道高反应性和支气管肺泡中性粒细胞增多的影响。一组5只犬在雾化生理盐水治疗前以及暴露于臭氧（3 ppm，1小时）后进行研究；另一组6只犬在氨溴索（1%溶液100次呼吸）治疗前以及暴露于臭氧后进行研究。每次研究时，我们测量气道对乙酰胆碱的反应性，并对支气管肺泡灌洗中的细胞进行计数。当给犬使用生理盐水安慰剂时，臭氧会导致气道对乙酰胆碱的反应性显著增加，以及气道中中性粒细胞大量涌入。当给犬使用氨溴索时，臭氧会导致支气管肺泡灌洗中中性粒细胞数量同样增加，但不会增加气道对乙酰胆碱的反应程度。我们得出结论，氨溴索可能通过抑制中性粒细胞中花生四烯酸氧化产物的形成和释放，来抑制犬臭氧诱导的气道高反应性。
