[Effects of H2 relaxin on airway remodeling and expression of cyclin D1 in a murine model of chronic asthma].

OBJECTIVE: To investigate the effects of H(2) Relaxin (Relaxin) on airway remodeling and the expression of cyclin D(1) in a murine model of chronic asthma. METHODS: Forty BALB/c mice were randomly divided into 4 groups:a normal control group, an asthma group, a vehicle control group and a relaxin treatment group, with 10 mice in each. The mice were sensitized and challenged with ovalbumin (OVA) to establish the chronic asthmatic model. The vehicle control group and the relaxin treatment group were subcutaneously injected with saline and relaxin (0.25 mg × kg(-1)× d(-1))respectively. Alteration of the airway inflammation and collagen deposition were observed by haematoxylin-eosin (HE) and Masson staining. Hydroxyproline in the lung was measured by enzyme linked immunosorbent assay (ELISA). The expression of α-smooth muscle actin (α-SMA) in lungs was evaluated by immunohistochemistry. The protein expression and the mRNA of cyclin D(1) were detected by Western blot and RT-PCR respectively. RESULTS: There were inflammatory cell infiltration, airway stenosis, bronchial smooth muscle hypertrophy and increased collagen deposition in the asthmatic group and the vehicle control group; but these changes were significantly ameliorated in the relaxin treatment group. The area of the α-SMA-stained smooth muscle layer in the asthmatic group and the vehicle control group was significantly greater than that in the control group (all P < 0.05), while administration of relaxin decreased the α-SMA immunostained area (all P < 0.05). The lung hydroxyproline content in the asthmatic and the vehicle groups [(0.68 ± 0.10) mg/g lung tissue, (0.67 ± 0.10) mg/g lung tissue] was significantly greater than that in the control group [(0.26 ± 0.05) mg/g lung tissue] (q = 16.61, 16.01 respectively, all P < 0.01). In contrast, treatment with relaxin significantly reduced the lung hydroxyproline content [(0.40 ± 0.06) mg/g lung tissue] compared with aforementioned 2 groups (q = 10.88, 10.26 respectively, all P < 0.05). The results of the Western blot analysis showed that the expression level of cyclin D(1) in the asthmatic and the vehicle groups [(1.38 ± 0.18), (1.50 ± 0.10)] was higher than that in the control group (0.38 ± 0.10) (q = 13.00, 14.65 respectively, all P < 0.05), while it was significantly decreased in the relaxin group (0.72 ± 0.13) (q = 8.51, 10.16 respectively, all P < 0.05). There were no differences in all of the parameters between the asthmatic group and the vehicle group (P > 0.05). CONCLUSION: Relaxin alleviated airway inflammation, airway smooth muscle thickening and airway remodelling in a murine model of chronic asthma, partially by down-regulating the expression level of cyclin D(1).