Pappová L, Jošková M, Kazimierová I, Šutovská M, Fraňová S
Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, and Biomed, Martin, Slovakia.
Department of Pharmacology, Jesseniu Faculty of Medicine in Martin, Comenius University in Bratislava, 4C Malá Hora, Martin, 036 01, Slovakia.
Adv Exp Med Biol. 2016;935:25-34. doi: 10.1007/5584_2016_24.
The aim of this study was to determinate bronchodilator, antitussive, and ciliomodulatory activity of inhaled combination therapy with budesonide and salmeterol, and to correlate the results with the anti-inflammatory effect. The experiments were performed using two models of allergic inflammation (21 and 28 days long sensitization with ovalbumine) in guinea pigs. The animals were treated daily by aerosols of budesonide (1 mM), salmeterol (0.17 mM), and a half-dose combination of the two drugs. Antitussive and bronchodilator activities were evaluated in vivo. The ciliary beat frequency (CBF) was assessed in vitro in tracheal brushed samples, and inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, and TNF-α) were determined in bronchoalveolar lavage fluid (BALF). We found that the combination therapy significantly decreased the number of cough efforts, airway reactivity, and the level of inflammatory cytokines in both models of allergic asthma. Three weeks long sensitization led to an increase in CBF and all three therapeutic approaches have shown a ciliostimulatory effect in order: salmeterol < budesonid < combination therapy. Four weeks long ovalbumine sensitization, on the other hand, decreased the CBF, increased IL-5, and decreased IL-13. In this case, only the combination therapy was able to stimulate the CBF. We conclude that a half-dose combination therapy of budesonide and salmeterol shows comparable antitussive, bronchodilator, and the anti-inflammatory effect to a full dose therapy with budesonide alone, but had a more pronounced stimulatory effect on the CBF.
本研究的目的是测定布地奈德和沙美特罗吸入联合疗法的支气管扩张、镇咳和纤毛调节活性，并将结果与抗炎作用相关联。实验使用豚鼠的两种变应性炎症模型（用卵清蛋白致敏21天和28天）进行。动物每天接受布地奈德（1 mM）、沙美特罗（0.17 mM）气雾剂以及两种药物的半剂量组合治疗。在体内评估镇咳和支气管扩张活性。在气管刷检样本中体外评估纤毛摆动频率（CBF），并在支气管肺泡灌洗液（BALF）中测定炎性细胞因子（IL-4、IL-5、IL-13、GM-CSF和TNF-α）。我们发现联合疗法在两种变应性哮喘模型中均显著降低咳嗽次数、气道反应性和炎性细胞因子水平。三周的致敏导致CBF增加，并且所有三种治疗方法均按以下顺序显示出纤毛刺激作用：沙美特罗＜布地奈德＜联合疗法。另一方面，四周的卵清蛋白致敏降低了CBF，增加了IL-5，并降低了IL-13。在这种情况下，只有联合疗法能够刺激CBF。我们得出结论，布地奈德和沙美特罗的半剂量联合疗法显示出与单独使用布地奈德全剂量疗法相当的镇咳、支气管扩张和抗炎作用，但对CBF具有更明显的刺激作用。
