Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison
Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison
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DOI：
10.1183/09031936.00004907
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发表时间：
2007-10-01
影响因子：
24.3
通讯作者：
Zaagsma, J.
中科院分区：
文献类型：
--
作者：
Bos, I. S. T.;Gosens, R.;Zaagsma, J.
哮喘和慢性阻塞性肺病的慢性炎症驱动气道的病理结构重塑。使用噻托溴铵，最近发现乙酰胆碱在持续过敏性哮喘豚鼠模型的气道平滑肌重塑中发挥主要调节作用。本研究的目的是研究气道重塑的其他方面，并比较噻托溴铵和糖皮质激素布地奈德的有效性。卵清蛋白致敏豚鼠用雾化卵清蛋白激发12周，卵清蛋白诱导气道平滑肌增厚，气管平滑肌过度收缩，肺收缩蛋白增加，肺组织中的蛋白质含量（平滑肌肌球蛋白）丰度、粘液腺肥大、粘蛋白5亚型A和C（MUC5AC）阳性杯状细胞数量增加和嗜酸性粒细胞增多。先前报告噻托溴铵治疗可抑制气道平滑肌增厚和收缩蛋白表达，并预防气管过度收缩。本研究表明，噻托溴铵还可完全预防过敏原诱导的粘液腺肥大，并部分降低MUC5AC阳性杯状细胞数量和嗜酸性粒细胞浸润的增加。布地奈德治疗还可预防气道平滑肌增厚、收缩蛋白表达、气管过度收缩和粘液腺肥大，并部分减少MUC5AC阳性杯状细胞数量和嗜酸性粒细胞增多。这项研究表明，噻托溴铵和布地奈德在抑制气道重塑的几个方面具有相似的效果，进一步证明噻托溴铵的有益作用可能超过支气管扩张。
Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide.Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin.The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia.This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.