氨溴索对慢性阻塞性肺疾病大鼠模型气道重塑的干预研究

目的 探讨转化生长因子β1(transforming growth factor-β1,TGF-β1)在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠模型肺内表达与气道重塑的关系以及氨溴索的干预作用.方法 气管内注入脂多糖以及熏香烟法建立大鼠COPD模型,干预组于模型建立后腹腔注射氨溴索溶液.观察病理特点,测定血气以及支气管肺组织匀浆羟脯氨酸含量,检测支气管管壁厚度和内周长,用原位杂交法检测TGF-β1基因表达的相对含量.结果 与对照组比较,模型组支气管肺组织羟脯氨酸含量显著增高(P<0.01).支气管管壁厚度显著增加(P<0.01),TGF-β1在支气管肺组织的表达增强(P<0.01),且TGF-β1基因表达的相对含量与支气管管壁厚度以及肺组织羟脯氨酸含量呈显著正相关(r=0.949,P<0.01;r=0.932,P<0.01).与模型组比较,氨溴索干预组支气管肺组织羟脯氨酸含量、支气管管壁厚度、TGF-β1在支气管肺组织的表达强度有减少趋势.结论 TGF-β1在气道重塑中起重要作用.应用氨溴索可以明显抑制COPD气道炎症及其气道重塑.

Experimentmental study on Inhibition of ambroxol in airway remodeling of chronic obstructive pulmonary disease rat models

Objective To evaluate the effect of ambroxol on chronic obstructive pulmonary disease (COPD) rat models and study the expression of transforming growth factor-β1 (TGF-β1) in the lung tissue of COPD. Methods COPD rat model was established by intratracheal instillation of lipopolysaccharide and cigarette smoking inhalation. The drug intervention group received daily inhalation of ambroxol since the first day. Pathologic study of the airway and lung tissue and blood gas analysis were performed. The levels of hydroxyproline in bronchi and lung homogenates were determined. The thickness of the small bronchial wall and the internal perimeter were measured. Also the gene relative content of TGF-β1 in the lung were determined. Results As compared to control group, the hydroxyproline level and the thickness of the bronchial wall of model group were significantly increased, the relative contents for TGF-β1 in the bronchi and lung of the model group were significantly higher. The changes in histopathology and blood gas, the relative contents for TGF-β1, the hydroxyprolive level and the thickness of the bronchial wall of ambroxol prevention group were significantly lower than those of model group. Conclusions The increased expression of TGF-β1 in COPD rat suggested of its role of remodeling in the airway wall. Inhalation of ambroxol inhibits airway wall remodeling on COPD model.