The Influence Of Ambroxol And Varenicline Tartrate On Expression Of TGF-β1 And IκBα In Rats With Chronic Bronchitis Induced By Smoking

Aims: To explore the roles of TGF-β1 and IκBαon airway inflammation in rats with chronic bronchitis induced by smoking and study the effects and mechanism of anti-inflammation of pretreatment with ambroxol and varenicline tartrate.Methods: Seventy five male Wistar rats were randomly divided into five groups: the normal group, the model group, high dose ambroxol intervention group(High group),low dose ambroxol intervention group(Low group) and the varenicline tartrate intervention group(VT group). The rats with chronic bronchitis in the model group were established by smoking for 76 days, six days each week, twice one day. For High group, rats were pretreated with ambroxol through peritoneal injection at 75mg·kg-1·d-1 before smoking every day. For Low group rats were pretreated with ambroxol at 30mg·kg-1·d-1 before smoking every day. For the model group, rats were pretreated with normal saline through peritoneal injection as much as the low dose ambroxol intervention group. The VT group was established by smoking (38 days) and by no-smoking (38 days). During no-smoking for 38 days, the VT group was treated by varenicline tartrate through oral administration, twice one day, at 0.05mg·kg-1. After 76 days, all of rats were killed. The bronchopulmonary histopathologic changes in hemotoxylin-eosin (HE) were seen under optical microscope. White cell count and White cell differential count were enumerated in bronchoalveolar lavage fluid (BALF). The expression of TGF-β1 and IκBαwere detected by immunohistochemistry.Results: The bronchopulmonary pathological changes in the model group were consistent with that of chronic bronchits. Bronchoalveolar lavage fluid (BALF): white cell count and the neutrophilic granulocyte count in the model group were significantly increased compared with the normal group (P<0.05), which significantly decreased in the other three intervention groups. Macrophagocyte count in the model group was significantly reduced compared with the normal group (P<0.05), which significantly increased in the other three intervention groups. The expression of IκBαin the model group was significantly reduced compared with the normal group (P<0.05), which significantly increased in the other three groups. The expression of IκBαin the High group was increased compared with the Low group (P<0.05). The expression of IκBαin the High group and Low group were increased compared with the VT group (P<0.05). The expression of TGF-β1 in the model group was significantly increased compared with the normal group (P<0.05), which significantly reduced in the other three intervention groups. The expression of TGF-β1 in the High group reduced compared with the Low group (P<0.05). The expressions of TGF-β1 in the High group and Low group were reduced compared with the VT group (P<0.05).Conclusions: Down-regulating the expression of IκBαand up-regulating the expression of TGF-β1 may be involved in the process of airway inflammation in rats with chronic bronchitis induced by smoking; high dose ambroxol and low dose ambroxol might have better effects on ameliorating airway inflammation by up-regulating the expression of IκBαand down-regulating the expression of TGF-β1 than varenicline tartrate ; ambroxol has the dose-effect on anti-inflammatory therapy.