Kamachi A, Munakata M, Nasuhara Y, Nishimura M, Ohtsuka Y, Amishima M, Takahashi T, Homma Y, Kawakami Y
First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.
Thorax. 2001 Jan;56(1):19-24. doi: 10.1136/thorax.56.1.19.
Goblet cell hyperplasia (GCH) is a prominent feature in animal models of atopic asthma produced by immunisation and following multiple challenges with antigens. The aim of this study was to examine the effect of a beta(2) agonist on the development of GCH induced by the immune response.
Brown Norway rats were immunised and challenged with an aerosol of ovalbumin for four weeks. Salbutamol (0.5 mg/kg/day) or vehicle was continuously delivered for the four weeks using a subcutaneously implanted osmotic minipump. The density of goblet cells, other morphological changes, and airway responsiveness to methacholine were evaluated 24 hours after the final challenge.
Treatment with salbutamol induced a more than twofold increase in the mean (SE) number of goblet cells (53.7 (7.3) vs 114.5 (11.8) cells/10(3) epithelial cells, p<0.01) while it did not significantly influence airway wall thickening and eosinophilic infiltration. Airway responsiveness to methacholine expressed as the logarithmic value of the concentration of methacholine required to generate a 50% increase in airway pressure (logPC(150)Mch) was also enhanced by the beta(2) agonist (-0.56 (0. 21) vs -0.95 (0.05), p<0.05). Additional experiments revealed that the same dose of the beta(2) agonist alone did not cause GCH in non-immunised rats and that the enhancement of GCH by salbutamol was completely abolished by simultaneous treatment with methylprednisolone (0.5 mg/kg/day).
These data suggest that salbutamol enhances goblet cell hyperplasia and airway hyperresponsiveness in this rat model of atopic asthma.
杯状细胞增生（GCH）是免疫接种及多次抗原激发所诱导的特应性哮喘动物模型的一个显著特征。本研究旨在探讨β₂受体激动剂对免疫反应诱导的GCH发展的影响。
用卵清蛋白气雾剂对棕色挪威大鼠进行免疫接种并激发4周。使用皮下植入的渗透微型泵持续4周给予沙丁胺醇（0.5毫克/千克/天）或赋形剂。在末次激发后24小时评估杯状细胞密度、其他形态学变化以及气道对乙酰甲胆碱的反应性。
沙丁胺醇治疗使杯状细胞平均（标准误）数量增加了两倍多（53.7（7.3）对114.5（11.8）个/10³上皮细胞，p<0.01），而对气道壁增厚和嗜酸性粒细胞浸润无显著影响。β₂受体激动剂还增强了气道对乙酰甲胆碱的反应性，以产生气道压力增加50%所需的乙酰甲胆碱浓度的对数值（logPC₅₀Mch）表示（-0.56（0.21）对-0.95（0.05），p<0.05）。额外实验显示，相同剂量的β₂受体激动剂单独应用于未免疫大鼠不会导致GCH，且沙丁胺醇对GCH的增强作用可被同时给予甲泼尼龙（0.5毫克/千克/天）完全消除。
这些数据表明，在该特应性哮喘大鼠模型中，沙丁胺醇可增强杯状细胞增生和气道高反应性。
