집먼지 진드기(Dermatophagoides farinae)로 감작한 백서천식모델 개발

Abstract

BACKGROUND: Animal models of human diseases have been used for research of pathophysiology of the diseases, development of new drugs or new therapeutic modalities in the medical field. In fact, there have been many experiments using animals to investigate the pathophysiology of asthma and allergy. Specific allergen sensitized animal models of asthma have been established mainly by using ovalumin. There are, however, only a few animal studies using house dust mites (HDM) which are the most common inhalant allergen in human atopic asthma. OBJECTIVE: This study aimed to establish an animal model of asthma using Sprague-Dawley (SD) rats with HDM sensitization. METHOD: First, 100microgram of HDM (Dermatophagoides farinaenae) crude extract was injected intraperitoneally on day 1 and day 3 with 1% aluminum hydroxide solution for allergen sensitization. In order to measure airway responsiveness, a single chamber plethysmography was used which was a non-invasive procedure. Two weeks after HDM sensitization, the inhaled allergen challenge test with an extract of HDM (Dermatophagoides farinae; 0.1% w/v in normal saline) was performed. Thereafter, the methacholine challenge test was performed three times before, one day and seven days after allergen challenge for the evaluation of airway hyperresposiveness. The rats were sacrified for the histological examination of eosinophilic infiltrations in their airways and lung tissues. RESULT: All of HDM sensitized 9 SD rats showed specific airway bronchoconstriction by an inhaled allergen challenge. The time to achieve 200% Penh increment was 13.4+/-12.8 minutes. In the methacholine challenge test, they showed that airway hyperresponsiveness was increased two-fold more on one day after the inhaled allergen challenge than before the challenge. It was, however, recorverd one week after the inhaled allergen challenge. On a histological examination of lung tissues, eosinophilic infiltrations were noted in small airways including respiratory bronchiols, alveoli with mucus impactions and interstitial tissues among alveoli. There were no eosinophilic infiltrations at large airways. CONCLUSION: An asthma animal model induced by HDM extract could be developed with SD rats which were sensitized with crude extracts of Dermatophagoides farinae by the intraperitoneal injection. This animal model of asthma is good to use for the studies of allergen related airway hyperresponsiveness. Furthermore it will be a helpful tool to explain the pathophysiology and investigate a new therapeutic modality of human asthma.