气道局部治疗对气道黏液高分泌干预作用的对比研究

A comparative study on airway local therapy inhibiting airway mucous hypersecretion

目的探讨常用局部治疗性药物对慢性气道黏液高分泌作用的机制和特点。方法用超声雾化吸入中性粒细胞弹性蛋白酶(NE)复制慢性支气管炎动物模型,分别吸入糖皮质激素布地奈德(budesonide)、胆碱M受体阻断剂异丙托溴铵以及两者配伍联用进行干预,用酶联免疫吸附试验(ELISA)及斑点印迹法分别检测大鼠支气管肺泡灌洗液(BALF)中黏蛋白(MUC)的含量和MUC5ACmRNA表达水平。结果NE能显著增加气道MUC和MUC5ACmRNA的表达(P<0.01);普米克令舒和异丙托溴铵均可降低MUC和MUC5ACmRNA的表达(P<0.05),两者联用可增强抑制黏蛋白的效应(P<0.01)。结论NE是慢性气道黏液高分泌发生的重要因素;布地奈德和异丙托溴铵可抑制MUC基因及转录水平的表达,且两者联用有协同效应。

Objective To explore the mechanism and characteristics of common local therapeutic drugs on chronic airway mucous hypersecretion in chronic bronchitis. Methods The rats with chronic bronchitis were pretreated with inhalation of neutrophil elastase by ultrasound atomization. Glucocorticoid budesonide and M-recepter antagonist ipratropium bromied (atrovent) single and the combination of them were inhaled by the rats. The levels of mucin (MUC) in bronchoalveolar lavage fluid (BALF) and MUC5AC mRNA in lung tissues were detected with ELISA and dot blotting respectively. Results Neutrophil elastase increased apparently the content of mucin and the expression of MUC5AC mRNA (P<0.01). Budesonide and atrovent could reduce the levels of mucin and MUC5AC mRNA(P<0.05).Budesonide in company with atrovent could reinforce the effects on mucins and MUC5AC mRNA (P<0.01). Conclusion Neutrophil elastase is an important factor in the development of airway mucous hypersecretion, budesonide and atrovent could inhibit the mucin release and MUC5AC mRNA expression, and reduce airway mucous hypersecretion. The combination of them could have synergistic effect.