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沙美特罗对慢性阻塞性肺疾病和肺炎患者纤毛及黏液的影响。

Effects of salmeterol on cilia and mucus in COPD and pneumonia patients.

作者信息

Piatti G, Ambrosetti U, Santus P, Allegra L

机构信息

Institute of Respiratory Diseases, Ospedale Maggiore di Milano, University of Milan, Via F. Sforza 35, 20122 Pad. Litta, Italy.

出版信息

Pharmacol Res. 2005 Feb;51(2):165-8. doi: 10.1016/j.phrs.2004.07.006.

Abstract

The present study was performed to evaluate the effects of salmeterol xynaphoate on ciliary beat frequency (CBF) of nasal epithelium and on rheological parameters of tracheobronchial mucus. We studied 10 steady-state COPD patients, eight patients with community-acquired pneumonia and eight healthy subjects as controls. They underwent a nasal brushing of the inferior turbinate to study the CBF in basal conditions and following application of salmeterol at 10(-5), 10(-6), 10(-7) and 10(-8) M concentrations directly to the epithelial samples. We also collected sputum samples, in COPD patients only, by the technique for "protected expectoration" for the rheological assessment in basal conditions and following addition of salmeterol at 10(-5), 10(-6), 10(-7) and 10(-8) M concentrations. Only samples with basal viscosity values higher than 2000 mPa/s were admitted. Our results confirmed previous studies that demonstrate a ciliostimulating effect induced by salmeterol. The mean basal CBF was 11.18 +/- 0.75 Hz in control subjects, while the pathological subjects showed a markedly lower basal values: 8.64 +/- 0.88 Hz (p = 0.000) and 8.83 +/- 0.68 Hz (p = 0.000), in COPD and pneumonia patients, respectively. Salmeterol induced ciliostimulation in both patients groups as well as the healthy controls. The maximum increase in CBF, highly significant, was obtained at 10(-6) M concentrations of salmeterol, while this effect decreased at lower concentrations. Regarding the action of salmeterol on rheological parameters, a direct effect of salmeterol on mucus cannot been demonstrated and the described beneficial clinical effects on mucociliary clearance occurring in vivo are probably related to an indirect effect of stimulation of ciliary beat. This preliminary study suggests that, in addition to COPD, salmeterol could be a useful therapeutic agent in pneumonia also, for its positive effect on ciliary movement other than bronchodilation, but this finding needs further investigations.

摘要

本研究旨在评估昔萘酸沙美特罗对鼻黏膜上皮纤毛摆动频率(CBF)以及气管支气管黏液流变学参数的影响。我们研究了10例稳定期慢性阻塞性肺疾病(COPD)患者、8例社区获得性肺炎患者以及8例健康受试者作为对照。他们接受了下鼻甲的鼻黏膜刷检,以研究基础状态下以及分别将浓度为10(-5)、10(-6)、10(-7)和10(-8) M的昔萘酸沙美特罗直接应用于上皮样本后的CBF。我们还仅在COPD患者中通过“保护性咳痰”技术收集痰液样本,用于基础状态下以及添加浓度为10(-5)、10(-6)、10(-7)和10(-8) M的昔萘酸沙美特罗后的流变学评估。仅纳入基础黏度值高于2000 mPa/s的样本。我们的结果证实了先前的研究,即昔萘酸沙美特罗具有纤毛刺激作用。对照组受试者的平均基础CBF为11.18±0.75 Hz,而COPD患者和肺炎患者的病理受试者基础值明显更低,分别为8.64±0.88 Hz(p = 0.000)和8.83±0.68 Hz(p = 0.000)。昔萘酸沙美特罗在两组患者以及健康对照组中均诱导了纤毛刺激。在昔萘酸沙美特罗浓度为10(-6) M时获得了CBF的最大增加,且具有高度显著性,而在较低浓度时这种作用减弱。关于昔萘酸沙美特罗对流变学参数的作用,无法证明昔萘酸沙美特罗对黏液有直接作用,并且体内所描述的对黏液纤毛清除的有益临床作用可能与刺激纤毛摆动的间接作用有关。这项初步研究表明,除COPD外,昔萘酸沙美特罗对纤毛运动有积极作用,除支气管扩张外,在肺炎中也可能是一种有用的治疗药物,但这一发现需要进一步研究。

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