Bos I S T, Gosens R, Zuidhof A B, Schaafsma D, Halayko A J, Meurs H, Zaagsma J
Department of Molecular Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Eur Respir J. 2007 Oct;30(4):653-61. doi: 10.1183/09031936.00004907. Epub 2007 May 30.
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.
哮喘和慢性阻塞性肺疾病中的慢性炎症会导致气道发生病理性结构重塑。最近在豚鼠持续性过敏性哮喘模型中，通过使用噻托溴铵发现乙酰胆碱在气道平滑肌重塑中起主要调节作用。本研究的目的是调查气道重塑的其他方面，并比较噻托溴铵与糖皮质激素布地奈德的疗效。用雾化卵清蛋白对卵清蛋白致敏的豚鼠进行12周的激发。卵清蛋白可导致气道平滑肌增厚、气管平滑肌高反应性、肺收缩蛋白（平滑肌肌球蛋白）丰度增加、黏液腺肥大、黏蛋白5AC和5C亚型（MUC5AC）阳性杯状细胞数量增加以及嗜酸性粒细胞增多。此前有报道称，噻托溴铵治疗可抑制气道平滑肌增厚和收缩蛋白表达，并预防气管高反应性。本研究表明，噻托溴铵还能完全预防变应原诱导的黏液腺肥大，并部分减少MUC5AC阳性杯状细胞数量的增加和嗜酸性粒细胞浸润。布地奈德治疗也可预防气道平滑肌增厚、收缩蛋白表达、气管高反应性和黏液腺肥大，并部分减少MUC5AC阳性杯状细胞数量和嗜酸性粒细胞增多。本研究表明，噻托溴铵和布地奈德在抑制气道重塑的多个方面同样有效，这进一步证明了噻托溴铵的有益作用可能超过支气管扩张作用。
