[Effects of H2 relaxin on the expression of Epac in a murine model of chronic asthma].

Objective: To explore the effects of H(2) relaxin on the expression of exchange protein directly activated by cyclic adenosine monophosphate (Epac) in a murine model of chronic asthma and the roles in the management of airway remodelling.

Methods: Thirty-two BALB/c mice were randomly divided into 4 groups of normal control, asthma, vehicle control and relaxin treatment (n = 8 each). They were sensitized and challenged with ovalbumin to establish a chronic asthmatic model. The vehicle control and relaxin treatment groups were subcutaneously injected with saline and relaxin (0.25 mg×kg(-1)×d(-1)) respectively. Alteration of airway inflammation was observed by hematoxylin-eosin (HE) staining. The airway expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were evaluated by immunohistochemistry. The protein expression of Epac and phosphorylated extracellular signal regulated kinases1/2 (p-ERK1/2) were detected by Western blot.

Results: Compared to those in the normal control group, massive infiltration of inflammatory cells, airway stenosis, bronchial smooth muscle hypertrophy were present in the asthmatic and vehicle control groups. The above-mentioned changes were significantly ameliorated in the relaxin treatment group. The percentage of PCNA positive cells (34.8% ± 6.1%, 33.5% ± 6.6%) and the expression of α-SMA ((1.70 ± 0.25), (1.54 ± 0.24) µm(2)/µm) in the asthmatic and vehicle control groups were significantly higher than those in the normal control group (9.9% ± 2.6%, (0.51 ± 0.16) µm(2)/µm) (all P < 0.05) while administration of relaxin decreased the airway expression levels of PCNA and α-SMA (22.9% ± 5.2%, (1.06 ± 0.25) µm(2)/µm) (all P < 0.05). The results of Western blot showed that the expression levels of Epac in the asthmatic and vehicle groups (0.62 ± 0.12, 0.68 ± 0.11) were lower than those in the control group (1.50 ± 0.17) (all P < 0.05) while it significantly increased in the relaxin group (1.08 ± 0.15) (all P < 0.05). The levels of phosphorylation of ERK1/2 in the asthmatic and vehicle groups (1.45 ± 0.13, 1.36 ± 0.09) were higher than those in the control group (0.38 ± 0.17) (all P < 0.05) while it decreased in the relaxin treatment group (0.72 ± 0.06) (all P < 0.05). No differences existed in all parameters between the asthmatic and vehicle groups (P > 0.05).

Conclusion: Relaxin alleviates the airway inflammation and airway smooth muscle cell proliferation in a murine model of chronic asthma probably through activating Epac and inhibiting the phosphorylation of ERK1/2.