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

为阐明哮喘气道重塑的机制，建立了反复暴露卵清蛋白(OA)的慢性哮喘模型。通过对该模型的检验，得到了以下结果。1)在检测吸入抗原浓度的方案中，每隔一天暴露于0.1、1.0和5.0%的OA，共1个月。在这种情况下，只有1.0%和5.0%的OA暴露组才能观察到呼吸道上皮和管壁的增厚。这一结果提示吸入抗原的浓度在诱导气道重塑中起重要作用。2)在本实验大鼠哮喘模型中，反复染毒1个月可引起气道上皮细胞和管壁重塑，但未见气道平滑肌增厚。这一结果提示，气道上皮细胞重塑可能进一步发展为平滑肌重塑。3)杯状细胞增生是导致呼吸道上皮细胞增厚的因素之一。4)上皮杯状细胞数量与体内乙酰甲胆碱气道反应性呈显著负相关。5)在渗透压持续输注β_2受体激动剂和皮质类固醇的实验方案中，观察到β_2受体激动剂和皮质类固醇激素输注后对乙酰甲胆碱的气道反应性增强。然而，这些药物对呼吸道形态没有显著影响。

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.