[Therapeutic effects of Bacille Calmette-Guerin vaccine on asthma airway remodeling in rats and its mechanism].

ABSTRACT

OBJECTIVE: To explore the therapeutic effects and mechanism of Bacillus Calmette-Guerin (BCG) vaccine on airway remodeling in rats. METHODS: Forty male Wistar rats were randomly divided into 5 groups of control, asthma,BCG vaccine, dexamethasone and BCG vaccine plus dexamethasone (n = 8 each). The animals were then sensitized and challenged by ovalbum in to establish the asthmatic model. A subcutaneous injection of BCG vaccine 0.025 mg was administered for the BCG vaccine group and an intraperitoneal injection of dexamethasone 0.5 mg/kg for the dexamethasone group.In BCG vaccine plus dexamethasone group, the rats received a subcutaneous injection of BCG vaccine (0.025 mg) plus an intraperitoneal injection of dexamethasone (0.25 mg/kg). All treatments were offered at half an hour pre-atomization. The control rats received an aerosol inhalation of normal saline instead of ovalbum. The parameters of airway morphological changes and the degree of airway remodeling were analyzed with computer graphics. The levels of transforming growth factor beta 1 (TGF-ß1) in bronchoalveolar lavage fluid (BALF) and the expressions of E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin in lung tissue and sera were detected. RESULTS: In asthmatic rats, the thickness of airway wall and smooth muscle were more significant than those of the control group ((95.01 ± 0.48), (43.86 ± 0.51) vs (25.96 ± 0.42), (15.14 ± 0.18) µm). Compared with the control group, the levels of TGF-ß1 in BALF and sera were significantly higher ((10.05 ± 0.26), (75.67 ± 1.17) vs (1.53 ± 0.18), (22.24 ± 0.35) µg/L), the expression of E-cadherin significantly decreased (0.26 ± 0.03 vs 0.45 ± 0.04), while α-SMA and fibronectin significantly increased (0.54 ± 0.06,0.56 ± 0.06 vs 0.32 ± 0.04, 0.35 ± 0.06) (all P < 0.01); Notably, compared with the asthmatic group, the thickness of airway wall and smooth muscle ((58.46 ± 2.43),(49.51 ± 1.44), (49.63 ± 1.42) and (25.84 ± 0.54), (25.44 ± 0.40), (25.62 ± 1.17) µm) significantly decreased by the treatments of BCG vaccine, dexamethasone or BCG vaccine plus dexamethasone, the levels of TGF-ß1 in BALF and sera ((3.42 ± 0.18), (3.27 ± 0.34), (3.39 ± 0.26) and (37.61 ± 0.22), (35.65 ± 0.49), (36.22 ± 0.71) µg/L) significantly decreased, the expressions of E-cadherin (0.29 ± 0.04, 0.32 ± 0.04, 0.31 ± 0.03) significantly increased and α-SMA and fibronectin (0.40 ± 0.06, 0.35 ± 0.06, 0.40 ± 0.05 and 0.47 ± 0.03, 0.43 ± 0.06, 0.47 ± 0.04) significantly declined (all P < 0.01). Western blot showed the similar results. CONCLUSIONS: BCG vaccine alleviates airway epithelial cell injury and epithelial mesenchymal transition induced by TGF-ß1 through immunoregulation. It also reduces asthmatic airway remodeling with a combination of dexamethasone.