The Effect Of Ambroxol On The Expression Of AP-1 And CuZn-SOD In Lung Of Smoking Rats

Objective To evaluate the role of ambroxol in the course of treatment for oxidant/ antioxidant imbalance in chronic obstructive pulmonary disease(COPD)by observing the histopathology change,airway resistance and lung compliance and determining the expression of active protein-1(AP-1)and CuZn-superoxide dismutase(CuZn-SOD)protein and mRNA in bronchial epithelia and alveolar macrophage of cigarreate smoking rates.Methods 30 healthy male rats were divided into 3 groups randomly:control group,smoking group and ambroxol treatment group,10 rats were in each group.Rat smoking device was made by ourselves.Establish smoking rate models through breathing in cigarette smoke for 12 weeks continuously.Ambroxol treatment group were given cigarette smoke as same as the smoking group and given ambroxol by intragastric administration from 5 weeks.Determine the airway resistance and pulmonary compliance of the rats,observe the histopathology change and detect the expression of AP-1 and CuZn-SOD protein and their mRNA using immunohistochemical method,immunocytochemical method and in-situ hybridization respectively.Results1 Histopathology change The typical pathologic change of emphysema was emerged in smoking group,and the change was gently in ambroxol treatment group.2 Airway resistance and pulmonary compliance The airway resistance were increased significantly and the pulmonary compliance were decreased significantly in smoking group (0.567±0.032,0.439±0.040)and ambroxol treatment group(0.387±0.016,0.535±0.066)as compared to control group(0.274±0.021,0.603±0.047)(P＜0.01);The airway resistance were decreased significantly and pulmonary compliance were increased significantly in ambroxol treatment group as compared to smoking group(P＜0.01).3 The expression of AP-1 protein in bronchial epithelia and alveolar macrophage The expression of c-Jun(29.99±2.56,27.07±2.27)and c-Fos(30.96±1.93,28.08±2.53)protein in bronchial epithelia and alveolar macrophage of smoking group were increased significantly as compared to control group(11.23±1.77,11.06±1.56;7.87±1.65,7.70±1.96)(P＜0.01);The expression of c-Jun(23.14±3.16,17.90±2.72)and c-Fos(24.02±3.16,21.10±2.67)protein of ambroxol treatment group were decreased significantly as compared to smoking group(P＜0.01).4 The expression of AP-1 mRNA in alveolar macrophage The expression of c-Jun (15.17±1.83)and c-Fos(15.64±1.87)mRNA in alveolar macrophage of smoking group were increased significantly as compared to control group(5.64±1.12,4.00±0.93)(P＜0.01);The expression of c-Jun(9.94±1.55)and c-Fos(10.07±2.43)mRNA of ambroxol treatment group were decreased significantly as compared to smoking group(P＜0.01).5 The expression of CuZn-SOD protein in bronchial epithelia and alveolar macrophage The expression of CuZn-SOD protein in bronchial epithelia(13.57±1.35)and alveolar macrophage(14.90±2.81)of smoking group were increased significantly as compared to controlgroup(11.46±1.86,12.28±2.39)(P＜0.05);The expression of CuZn-SOD protein of ambroxol treatment group(12.19±1.43,14.06±2.58)were not decreased significantly as compared to smoking group(P＞0.05).6 The expression of CuZn-SOD mRNA in alveolar macrophage The expression of CuZn-SOD mRNA in alveolar macrophage of smoking group(23.54±2.88)were increased significantly as compared to control group(5.80±1.65)(P＜0.01);The expression of CuZn-SOD mRNA of ambroxol treatment group(16.31±2.94)were decreased significantly as compared to smoking group(P＜0.01).Conclusion Ambroxol can improve the pulmonary function and reduce emphysema change of smoking rats;The expressioin of AP-1 and CuZn-SOD were decreased in bronchial epithelia and alveolar macrophage of smoking rates after treatment with ambroxol,Ambroxol may play a certain role in the antioxidant therapy of COPD through dow regulating the expression of AP-1.