Effects of Ipratropium Bromide Atomizing Liquid on Lung Function and Airway Remodeling in Rats with Chronic Obstructive Pulmonary Disease via TGF-β1/Smads Signaling Pathway

OBJECTIVE To explore effects of ipratropium bromide atomizing liquid on lung function and airway remodeling in rats with chronic obstructive pulmonary disease(COPD) and its regulation on transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 2/3(Smad 2/3) signaling pathway. METHODS According to the random number table method, the SD rats were divided into normal group, model group, experimental group, and positive control group, each with 15 rats. The rats in the model group, experimental group and positive control group were smoked with Taishan jasmine cigarettes method to replicate the COPD rat model:the rats were put into a smoking box, 15 Taishan jasmine cigarettes were lightened for 1 h, 3 times a day for 90 consecutive days. The rats in the normal group do not smoke. After successfully replicating the COPD model, rats in the experimental group inhaled ipratropium bromide solution 1 mg/4 mL with a nebulizer in a self-made small animal airtight box, once a day for 2 h each time, rats in the positive control group were injected subcutaneously with TGF-β1 inhibitor LY2157299(20 mg·kg^-1), once a day, rats in the normal group and model group were injected subcutaneously with equal doses of normal saline. After 28 days of administration, the pulmonary function of each group of rats was sequentially tested using a small and micro animal pulmonary function tester. TUNEL staining was used to detect the apoptosis in the lung tissues of rats in each group, and immunofluorescence was used to detect the expression of the airway remodeling marker protein α-smooth muscle actin(α-SMA) in the lung tissues of the rats in each group. Western blotting was used to detect the expression of TGF-β1 and p-Smad2/3 in the lung tissues of rats in each group. RESULTS Compared with the normal group, the respiratory rate, the apoptosis rate of lung tissue, the fluorescence intensity of α-SMA, the expression of TGF-β1 and p-Smad2/3 in the model group appeared a significant increase(all P<0.05), the rat's ventilation and tidal volume appeared a significant decreased (all P<0.05). Compared with the model group, the respiratory rate, the apoptosis rate of lung tissue, the fluorescence intensity of α-SMA, the expression of TGF-β1 and p-Smad2/3 in the experimental group and the positive control group appeared significantly decreased(all P<0.05), and the rats' ventilation and tidal volume appeared increased significantly(all P<0.05). CONCLUSION Ipratropium bromide can inhibit lung cell apoptosis, relieve airway remodeling in COPD rats, and improve lung function. This may be related to the inhibition of TGF-β1/Smads pathway.