The Expressions Of Nuclear Factor-kappa B And Tumor Necrosis Factor-alpha In The Lung Tissue Of Chronic Obstructive Pulmonary Disease Rat Modelsand Effect Of Ambroxol On It

Background and objectiveChronic obstructive pulmonary disease(COPD) was a chronic respiratory internal disease. The chronic inflammation in airways and parenchyma plays a pivotal role in COPD.To establish chronic obstructive pulmonary disease rat models by smoking as well as intratracheal instillation lipopolysaccharide (LPS) respectively, and to study the role of nuclear factor- kappa B (NF-κB)and tumor necrosis factor-alpha(TNF-α) in chronic obstructive pulmonary disease (COPD),and the correlations among them and to explore the role of NF-κB and TNF-αin the pathogenesis of COPD and the effects of ambroxol on it.Materials and methodsWistar rats were randomly divided into three groups (Group A: Normal control group,Group B: model group,Group C: ambroxol treated group. The COPD rat models which were established by intratracheal instillation of 200ug lipopolysaccharide once for every two weeks(twice), and exposed to cigarette smoke for 2h/d for 30 days. Ambroxol was given to the rats of Group C through injection at a dose of 35mg/kg just before exposure to cigarete smoke everyday from the 16th day. Bronchial alveolar lavage(BAL) were performed as usual. Total cell counts and AM counts,PMN counts in BALF were counted using a hemacytometer. The pathological changes were observed. The expressions of NF-κB and TNF-αin lung tisse were detected by immunhistochemistry. The correlations among the expression of NF-κB and TNF-αin COPD model group and ambroxol treated group were analyzed. The third is that the data from the experiment were processed by using the SPSS10.0 statistical software and a equals 0.05 was taken as the testing standard of whether the difference having statistical significance.ResultsThe pathological changers of bronchi and lung tisse in COPD rat models were to those of COPD patients. Total cell couints,AM counts and PMN counts in BALF of COPD model group were significantly increased than those of control group(P<0.01).Total cell counts, AM counts and PMN counts in BALF of ambroxol treated group were significantly increased than those of control group(P<0.01).The expressions of NF-κB and TNF-αin COPD model group were significantly increased than those in control group(P<0.01).The expressions of NF-κB and TNF-αin ambroxol treated group were decresed than those in COPD model group(.P<0.05).Positive correlations were demontrate beween the expressions of NF-κB and TNF-αin COPD model group (r=0.905,P<0.01) and ambroxol treated group (r=0.883,P<0.01).Conclusion(1) The COPD models are made by the rats exposed to cigarette for 30 days as well as intratracheal instillation LPS twice,its pathological changes accorded with the human COPD.(2) The difference between NF-κB and TNF-αin each experiment group and control group have statistical significance, which proves that NF-κB and TNF-αis crucial in the formation of COPD.(3) Our data implied a close correlation between NF-κB,TNF-αand airway inflammation in COPD rat model,the synergy of NF-κB and TNF-αmay contribute to the development of COPD through activation of neutrophil into airway and be responsible for the persistence and amplification of airway inflammation in COPD.(4) Ambroxol may decrease the expression of NF-κB and TNF-αin COPD rat models,and may play an important role in the treatment of COPD.