Tamaoki J, Chiyotani A, Sakai N, Takeyama K, Konno K
First Department of Medicine, Tokyo Women's Medical College, Japan.
Thorax. 1993 May;48(5):542-6. doi: 10.1136/thx.48.5.542.
The effect of azelastine on airway mucociliary transport function was studied by measuring ciliary motility of human bronchial epithelium in vitro with a photoelectric method.
Bronchial epithelial cells were obtained by fibreoptic bronchoscopy, mounted in a Rose chamber, and perfused with Krebs-Henseleit solution. The preparations were placed on a microscope stage equipped with an illuminator, and the variations of light intensity caused by ciliary beating were detected by a photometer.
The addition of azelastine to the perfusate increased ciliary beat frequency (CBF) in a dose dependent manner without ciliary discoordination. The mean (SE) maximal increase from the baseline value and the concentration required to produce a half maximal effect were 27.0 (4.2)% and 9.2 x 10(-6) mol/l, respectively. Exposure of the cells to the perfusate containing 3 ppm sulphur dioxide rapidly decreased CBF by 59.2 (5.0)%, and was accompanied by a reduction in intracellular cyclic AMP levels from 38.1 (4.3) to 10.1 (2.4) pmol/mg protein. This effect was prevented by pretreatment of cells with azelastine in a dose dependent manner.
Azelastine not only stimulates ciliary motility of airway epithelium and hence mucociliary transport function, but may also protect against sulphur dioxide induced ciliary dysfunction, probably by inhibiting intracellular cyclic AMP loss.
采用光电法体外测量人支气管上皮细胞的纤毛运动,研究氮卓斯汀对气道黏液纤毛运输功能的影响。
通过纤维支气管镜获取支气管上皮细胞,将其置于罗斯小室中,并用克雷布斯-亨泽莱特溶液灌注。将标本置于配备有照明器的显微镜载物台上,用光度计检测纤毛摆动引起的光强度变化。
向灌注液中添加氮卓斯汀可使纤毛摆动频率(CBF)呈剂量依赖性增加,且无纤毛失调现象。相对于基线值的平均(标准误)最大增加量和产生半数最大效应所需的浓度分别为27.0(4.2)%和9.2×10⁻⁶mol/L。将细胞暴露于含3ppm二氧化硫的灌注液中,CBF迅速降低59.2(5.0)%,同时细胞内环磷酸腺苷水平从38.1(4.3)降至10.1(2.4)pmol/mg蛋白质。氮卓斯汀对细胞进行预处理可剂量依赖性地预防这种效应。
氮卓斯汀不仅能刺激气道上皮的纤毛运动,从而增强黏液纤毛运输功能,还可能通过抑制细胞内环磷酸腺苷的丢失来预防二氧化硫诱导的纤毛功能障碍。