Experimentmental Study On The Inhibition Of Ambroxol In The Airway Wall Remodeling Of COPD Rat Models

[Objective] To evaluate the effect of Ambroxol on chronic obstructive pulmonary disease(COPD) rat models and the expression and distribution of transforming growth factor- β₁(TGF- β ₁) in the lung tissue of COPD.[Methods] The COPD rat model was established by intratracheal instillation of lipopolysaccharide twice with simaltaneous daily exposure to cigarette smoking. 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 hydroxyprolive in bronchi and lung homogenates were determined by biochemical method. The thickness of the small bronchi wall and the internal perimeter were measured by computer image analyzer. Also the gene relative content of the TGF-β ₁ in the lung were determined by in situ hybridization.[Results] The changes in histopathology and blood gas in the animal model were similar to those in COPD patients. The hydroxyproline level of the model group was significantly increased as compared to the control group. The thickness of the bronchi wall was significantly increased in the COPD model as compared to the control group. The relative contents for TGF- β₁ in the epithelial cells of the bronchi, endothelial cells of the pulmonary arteries and alveolar macrophages of the model group were significantly higher than those of the control group. The changes in histopathology and blood gas, the relative contents for TGF- β₁, the hydroxyprolive level and the thickness of the bronchi wall of the Ambroxol prevention group were significantly lower than that of the model group.[Conclusion] The COPD model may be successfully established by intratracheal instillation of lipopolysaccaride twice with simaltaneous daily exposure to cigarette smoking. The increasing 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 human COPD and is worth of further observation.