OBJECTIVETo study the changes of Hes-1, the target gene of Notch signaling pathway, and its relationship with airway inflammation and remodeling in a rat model of asthma.

METHODSForty-eight rats were randomly divided into an asthma group and a control group. The rats in the asthma group were sensitized and challenged by ovalbumin (OVA), and normal saline was used in the control group. Two groups were further divided into 3 subgroups according to time points after challenging, i.e. 4 weeks, 8 weeks and 12 weeks (n=8 rats each). Pathological changes of lungs were observed by light microscopy and the thickness of bronchial smooth muscle layer (Wam) was measured. The levels of IL-4 and INF-γ in rat serum and bronchoalveolar lavage fluids (BALF) were measured using ELISA. Expression levels of Hes-1 protein and mRNA were determined by immunohistochemistry and quantitative real-time PCR respectively.

RESULTSTogether with the extension of challenging, the Wam of rats in the asthma group increased, a decrease of INF-γ level and an increase of IL-4 level in serum and BALF were also observed, and the differences were statistically significant compared with those in the corresponding control group (P<0.05). Hes-1 protein and mRNA levels also increased gradually after OVA challenging and were higher than those in the control group (P<0.05). The levels of Hes-1 protein and mRNA were positively correlated with Wam and IL-4 in serum and BALF, but were inversely correlated with INF-γ in serum and BALF (P<0.05).

CONCLUSIONSLevels of Hes-1 protein and mRNA increased, which were closely related with the levels of airway inflammatory factors and remodeling of airway smooth muscle. Hes-1 may play an important role in the pathogenesis of asthma.

Airway Remodeling ; Animals ; Asthma ; etiology ; Basic Helix-Loop-Helix Transcription Factors ; analysis ; genetics ; physiology ; Disease Models, Animal ; Homeodomain Proteins ; analysis ; genetics ; physiology ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Male ; Rats ; Rats, Sprague-Dawley ; Transcription Factor HES-1