Experimental Study On Expression Of Hypoxia Inducible Factor-1a In Bronchopulmonary Tissue In Asthmatic Rat Model

Objective: To establish the asthmatic model in rat; to investigate the expression of hypoxia inducible factor-1α(HIF-1α) in bronchopulmonary tissue in asthmatic rat model and its significance; to observe the expression of HIF-1αin asthmatic rat model treated with DXM.Methods: Thirty-two Wistar rats were divided randomly into normal control group, negative control group, asthma group and asthma treated with DXM groups. Asthma rat model was established by sensitization and stimulation with ovalbumin (OVA) conjuncted with Al(OH)3. Normal control group had no treatment. The negative control group was treated with saline. The DXM group was the asthmatic rats treated with DXM. The model was confirmed by pathological histologic section of the Hematoxylin and Eosin (HE) stain of bronchopulmonary tissue, and the observation of the symptoms of the rats after sensitization and stimulation with OVA. RT-PCR and Western-blot were used to evaluate the gene and protein expressions of HIF-1αin bronchopulmonary tissue in these groups.Result: The asthmatic rat model was established successfully. Histologic observations of the bronchopulmonary of asthma group showed bronchial constriction, bronchial epithelium denaturation and inflammatory cell such as eosinophils and polymorphonuclear leucocyte infiltration and recruiment in the bronchial lumen, eosinophils and lymphocytes infiltration around bronchial mucosa. Only a small amount number of inflammatory cell infiltration around the airways was found in control group. The asthmatic rats had the symptoms of restlessness, breathlessness, abdominal respiratory rhythms and wheezing rale after stimulating with OVA. These symptoms were not observed in normal control group and negative control group. The symptoms were much milder in DXM group than that in asthmatic group. Compared to the control group, the expression of HIF-1αboth in gene and protein levels significantly increased in asthma group (P<0.05, n=8). However, there was no significant difference between the control and negative group (P>0.05, n=8). The expression of HIF-1αin asthma group treated with DXM was significantly reduced when comparing to asthma group (P<0.05, n=8). But no significant difference of expression levels was detected between asthma group treated with DXM and control group, (P>0.05, n=8).Conclusion: The expression of HIF-1αincreased significantly in asthmatic rat model. Suggesting that HIF-1αmay be involved in asthmatic pathogenesis, and its expression level may be regulated by DXM. Therefore we provide direct evidence and a new therapeutic strategy for asthma.