[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.