| BackgroundAt present, asthma is thought to be a chronic inflammatory disorder of the airways in which many cells, such as eosinophils, mast cells, T lymphocytes, neutrophils, airway epithelial cells, etc., and cellular elements play a role. The interaction between these cells and cellular elements will perpetuate the airway inflammation. The longstanding and recurrent exacerbations of the inflammation will inevitably result in permanent structural changes of airways such as desquamation and hyperplasia of epithelium, basement membrane thickening, subepithelial fibrosis, hypertrophy/hyperplasia of airway smooth muscles, hyperplasia/metaplasia of goblet cells, submucus glands hyperplasia and hypertrophy, angiogenesis and remodeling of airway vasculature etc., known as airway remodeling, and at last lead to irreversible airway obstruction. Vascular reactions are central events in all kinds of inflammations. Angiogenesis and inflammation are codependent processes. Inflammation can promote angiogenesis, and new vessels may enhance tissue inflammation. Some forms of inflammation, especially chronic inflammation, can stimulate vessel growth. New vessels may contribute to a tissue's altered inflammatory response. So it is likely that their coexistence may lead to more severe, damaging, and persistent inflammation. It has been confirmed that angiogenesis and vascular remodeling are prominent features of asthmatic patients. But the mechanisms and consequences of the changes as well as possible therapeutic strategy targeted the changes are just beginning to be elucidated.Objective To observe the airway angiogenesis and elucidate its relation to the airway remodeling, its mechanisms and influence of glucocorticoid on it in a chronic asthmatic mouse model. MethodsThe development of chronic asthmatic miceWe developed a chronic asthmatic mouse model by repeatedly sensitized to allergen(OVA) with adjuvant intraperitoneally in which chronic airway inflammation is maintained by repeatedly challenged with OVA without adjuvant intratracheally. Twenty-four BALB/c mice were divided into three groups equally: normal control group, chronic asthmatic group, dexamethasone treated chronic asthmatic group. Mice in chronic asthmatic group were given 200(l 0.01% OVA (1mg OVA and 8ml Al(OH)3 per 10ml) intraperitoneally on days 0, 7, 14. Subsequently, they were challenged repetitively with 50(l 0.2% OVA without adjuvant intranasally on days 21～30, 48, 62 and 74～76. Mice in normal control group were sensitized and challenged with equal volume of NS on the same days. Chronic asthmatic mice in dexamethasone treated group received 2mg/kg dexamethasone intraperitoneally 1h before each challeng respectively, while mice in normal control group and chronic asthmatic group were given equal volume of NS intraperitoneally on the same time.Twenty-four hours after the last challenge the mice were killed by right eye removal. Blood were centrifuged and serums were stored at -20℃. Right lungs were lavaged and BALF were reserved similarly. Left lungs and tracheae were fixed with 10% buffered formalin and embedded in paraffin in 24h. Pathological slides were made from left lungs and tracheae and stained with hematoxylin-eosin. Also anti-Factor Ⅷ Ag antibodys were used to detect vessels.Count of density of vessels in tracheae and measurement of morphometric parameters of airway wallThe number of vessels in lamina propria and submucosa of tracheae in immunohistochemistry slides were counted microscopically(×1000). For each mouse five slides and ten non-overlapping high power fields where the number of vessels was as most as possible in each slide assessed. The results were added together expressed as the density of vessels(number of vessels/mm2).Bronchial walls without cartilage in haematoxylin-eosin stained sections were examined using a Leica Q500MC image analysis system. The airway wall basement membrane perimeter(Pbm) and total bronchial wall area(WAt) were measured and Pbm/WAt were calculated.Measurement of concentration of V...
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