| Backgroud Ashma is a chronic ariway inflammatory disorder charactered by eosinophil inflammation and airway hyperresponsiveness(AHR). Repeated exacerbations caused by chronic inflammation in asthma induced the irreversible thickeness in the airway wall. The increased thickness involves an increase in muscle mass, subepithelium collagen deposition, enhanced goblet cells hyperplasia/metaplasia and mucus hypersecretion and angiogenesis. The remodeling features result in irreversible airways obstruction which is usually associated frequency of wheezing and the ongoing presence of asthma. Moreover, studies in which lung function changes have been examined have shown that persistent asthma is often associated with an increase in the rate of decline in FEV1. The whole clinical characteristics of airway remodeling remain under full known. Few evidence has shown the prevention or therapeutics effect of existent anti-asthma medications. The airway remodeling may be a new target for the development of anti-asthma drugs. Before new drugs occurrence, to investigate the effect of early use of existent anti-asthma medications on the remodeling course will be very important. The clinical research has many defect for the difficulty in gaining the sample. So the animal models become the favorite objects.Objective To investigate the time course of airway remodeling in a mouse asthma model and establish a new asthma model to be provided with the human asthma pathologic character. Based on the new murine asthma model we will investigate the effect of Montelukast and Budesonide on the airway inflammation and remodeling course. Another purpose of this study was to compare the effects of treatment with Montelukast and Budesonide, alone or in combination. Hypothesis Allergen induced the airway inflammation and airway structure changes in sensitized mice. The structure changes include subepithelium collagen deposition, airway smooth musclehypertrophy/hyperplasia, goblet cells hyperplasia and mucus hypersecretion. The early occurred changes increase significantly when the exposure time elongate. Treated early with Montelukast or Budesonide could inhabit the inflammatory and structure changes. Combination of the two medications provide better effect than either use alone.Methods Male C57BL/6 mice were sensitized and challenged repeatedly by Ovalbumin(OVA). In different time point (2w, 4w, 6w, 8w, 12w) of the exposure course, the mice were killed and samples were collected. The eosinophils(Eos) numbers in bronchoalveolar lavage fluid (BALF), peripheral blood and bone marrow were counted. The IL-5 and IFN-y levels in supernatant were assayed. The outcomes in pulmonary histology include Eos counts and airway smooth muscle area in hematoxylin and eosin(H&E) stained sections, percent of goblet cells in total epithelial cells and the degree of mucus hypersecretion in Acian Blue-PAS(AB-PAS) stained sections, the morphometric analysis of collagen in Masson's trichrome stained sections. Further, the effect of single or combination of Montelukast and Budesonide on above changes were observed. Result1. Time course of the improved remodeling mouse model. Compared with the NS CONTROL group, the Eos counts in BALF, peripheral blood and bone marrow increase significantly (P<0.01) after repeated allergen challenge in sensitized mice. IL-5 levels in BALF and serum(P<0.01) increase and IFN-y in BALF decrease(P<0.01). The morphometric results include obvious Eos infiltration around the bronchus and increased airway smooth muscle mass in H&E stained sections, enhanced goblet cell hyperplasia mucus secretion in AB-PAS stained sections and excessive collagen deposition around the airway wall in Masson's trichrome stained sections. Morphometric quantitative analysis indicate the structure changes was obvious different compared with the NS CONTROL group(P<0.01) in the early stage of OVA exposure and increased significantly when the exposure time elongate(P<0.01).2. Effect of Montelukast and Budsonide on the airway inflammation and remode...
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