Relationship between Hes-1 and airway inflammation and remodeling in a rat model of asthma
2014
Objective To 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. Methods Forty-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. Results Together 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(P0.05). Hes-1 protein and mRNA levels also increased gradually after OVA challenging and were higher than those in the control group(P0.05). 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(P0.05). Conclusions Levels 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.
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