Study on the Mechanisms and Regulation of Airway Remodeling in Rat Chronic Asthma Model.

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To elucidate the mechanisms of airway remodeling in bronchial asthma, chronic asthma model with repeated ovalbumine (OA) exposure was developed. By examining this model, following results were obtained. 1) In the protocol examining the effects of inhaled antigen concentration, rats were exposed to 0.1,1.0 and 5.0% OA every other day for 1 month. In this setting, airway epithelial and wall thickening were observed only in 1.0 and 5.0% OA exposure groups. This result suggest that the concentration of inhaled antigen is important in inducing airway remodeling. 2) In present rat asthma model, repeated exposuure to OA for 1 month resulted airway epithelial and wall remodeling but airway smooth muscle thickening was not observed. This results suggest that airway epithelial remodeling may proceed to smooth muscle remodeling. 3) Goblet cell hyperplasia was revealed to be one of the factors responsible for airway epithelial thickening. 4) There was significant negative correlation between the number of goblet cells in the epithelium and in vivo methacholine airway responsiveness. 5) In the protocol examining the effects of continuous infusion of beta2-agonist and corticosteroid by osmotic pomp, enhanced airway responsiveness to methacholine was observed after beta2-agonist infusion. However, there was no significant effects of these drugs to airway morphology.