The Effect Of Inhaled Corticosteroids In Preventing And Treating Airway Remodeling Of The Asthmatic Model

Object Airway inflammation and remodeling is key characteristic of chronicasthma. Inhaled corticosteroids are the most important drugs for asthma at present. It is not clear whether inhaled corticosteroids can prevent airway remodeling. Object of this study was to investigate the effect of inhaled corticosteroids (ICS) on airway remodeling in guinea gig models of allergic asthma.Methods There are 108 guinea pigs, which were male, 400-500g weight anddivided into 3 groups randomly and equally: A group, B group, C group. A group was sensitized by intraperitoneal injection on Day l,two weeks later they were exposed to aerosolized 1%OVA (wt/vol) (Sigma, Inc.)for 30 minutes, one time every week from Week one to Week twelve. B group was treated with nebulized budesonide on the basis of A group, C group was sensitized and exposed to normal saline during the whole experiment. Every group was divided into 6 subgroups by time: 24 hours, 1 week, 2 weeks, 4 weeks, 8 weeks and 12 weeks.Every subgroup consists of 6 guinea pigs. Twenty-fours after the last OVA exposure at every phase, the guinea pigs were killed. Then the lung tissue specimens were collected, embedded in paraffin, sectioned and stained. Hematoxylin and eosin staining, collagen staining and immunoassaying were accomplished respectively. The expression of transforming growth factor-betal and matrix metalloproteinases-2 (MMP-2) was tested. The apoptosis of inflammatory cell was tested by TUNEL. The difference was analyzed in every group. The effects were determined that ICS prevented and treated the occurrence and development of airway remodeling in asthma.Results (1) A group presented much inflammatory cell infiltration, epithelial desquamation , airway smooth muscle hypertrophy, sub- epithelial fibrosis and bloodvessel hyperplasia after exposure for 12 weeks, there was significantly difference comparing with B% C group.(2) The expressing of MMP-2 and TGF significantly increased in A group, the apoptosis of inflammatory cell decreased in A group. (3) It was reduced that eosinophil infiltration, epithelial desquamation, airway smooth muscle hypertrophy, sub- epithelial fibrosis and blood vessel hyperplasia after exposure for 12 weeks, the expressing of TGF and MMP-2 significantly decreased in B group, but they increased comparing with C group. The apoptosis of inflammatory cell increased in B group. There was a little infiltration of inflammatory cell and no structure change above in C group.Conclusion (1) There was airway remodeling in guinea pig model of allergicasthma after exposure for 12 weeks, it included that epithelial desquamation, blood vessel hyperplasia, airway smooth muscle hypertrophy, sub- epithelial fibrosis after exposure for 12 weeks. (2) TGF and MMP-2 were involved in airway remodeling. (3) Inhaled corticosteroids can prevent airway remodeling in asthma, reduce the expressing of TGF-and MMP-2, but the effect is incomplete and they could partly inhibit airway structure change .(4) Inhaled corticosteroids can accelerate the apoptosis of inflammatory cell. (5) All kind of structure changes do not occur at the same time, for example the epithelial desquamation occurring after exposure for 1 week and sub- epithelial fibrosis occurring after exposure for 8 weeks, and it is incomplete that the prevention of inhaled corticosteroids on airway remodeling. So inhaled corticosteroids should be introduced to treat asthma as early as it possible.