盐酸氨溴索对吸烟大鼠肺内转化生长因子-β_1和γ-谷氨酰胺半胱氨酸合成酶表达的影响

目的观察盐酸氨溴索对吸烟大鼠气道上皮细胞和肺泡巨噬细胞转化生长因子-β1(TGF-β1)和γ-谷氨酰胺半胱氨酸合成酶(γ-GCS)表达的影响,探讨其在慢性阻塞性肺疾病抗氧化治疗中的作用。方法吸入香烟烟雾法建立大鼠模型,盐酸氨溴索灌胃吸烟大鼠,比较气道阻力、肺顺应性,测定气道上皮细胞、肺泡巨噬细胞TGF-β1、γ-GCS蛋白和mRNA的表达。结果氨溴索组较吸烟组肺顺应性增高,气道阻力降低(P<0.05)。吸烟组和氨溴索组气道上皮细胞和肺泡巨噬细胞TGF-β1和γ-GCS表达明显高于对照组(P<0.01);氨溴索组TGF-β1蛋白和mRNA表达均低于吸烟组(P<0.05),气道上皮γ-GCS蛋白以及肺泡巨噬细胞mRNA与吸烟组差异无统计学意义,而肺泡巨噬细胞γ-GCS蛋白表达高于吸烟组(P<0.05)。结论盐酸氨溴索改善吸烟大鼠肺功能,降低肺内TGF-β1表达,提高肺泡巨噬细胞γ-GCS蛋白含量,增强抗氧化能力。

The effects of ambroxol hydrochloride on transforming growth factor-β1 and γ-glutamylcysteine synthetase in lung of smoking rats

Objective. To investigate the effects of Ambroxol hydrochloride on the levels of transforming growth factor-β1 （TGF-β1） and γ-glutamylcysteine synthetase （γ-GCS） in smoking rats, and to explore the role of ambroxol as an antioxidant in treatment of COPD. Methods Wistar rats were exposed to cigarette smoke for construction of COPD models. In a group of rats, ambroxol galvage were given for 8 consecutive weeks starting from week 4. Data on expiratory airway resistance, lung compliance, expression of TGF-β1 and γ-GCS in airway endothelial cells and alveolar macrophages were compared among the normal controls, untreated models （smoking group） and ambroxol-treated rats （ambroxol group）. Results The expiratory airway resistance was increased and lung compliance decreased significantly in the smoking group and ambroxol group, while the ambroxol group showed lower airway resistance and higher lung compliance compared with the smoking group （P〈0.05）. The level of TGF-β1 and γ-GCS expressions in smoking group and ambroxol group was obviously increased compared with normal controls （P〈0.01）. The ambroxol group showed lower level of TGF-β1 mRNA and proteins （P〈0.05）, similar levels of γ-GCS protein in airway endothelial cell and γ- GCS mRNA in alveolar macrophages but higher level of γ-GCS protein in alveolar macrophages as compared with the smoking group （P〈0.05）. Conclusion In smoking rats, Ambroxol may result in improved lung function, decreased expression of TGF-β1 and increased level of γ-GCS protein in alveolar macrophage, suggesting its role as antioxidant in treatment of COPD.