Department of Pharmacology, Comenius University, Martin, Slovakia.
Adv Exp Med Biol. 2013;756:49-55. doi: 10.1007/978-94-007-4549-0_7.
The aim of the study was to prepare and evaluate the experimental model of allergic asthma. Changes in chough reflex, bronchoconstriction and the degree of inflammation were studied in ovalbumin (OVA) sensitized guinea pigs after 0, 7, 14, 21 days of exposure. The cough reflex was induced by citric acid inhalation in conscious animals in a double chamber body plethysmograph. Tracheal smooth muscle reactivity was assessed by examining the in vitro response to histamine (H) (10(-8)-10(-3) mol/l) and in vivo to H nebulization (10(-6) mol/l). BALF levels of IL-4, IL-5 and the eosinophil count were used as parameters of airway inflammation. After 7 days of OVA sensitization, there was an increase in tracheal smooth muscle contractility in vitro to cumulative concentration of H and an increase in cough parameters. After 14 days of OVA sensitization, there was a further increase in tracheal smooth muscle contractility to H, an increase in airway resistance, and a small increase in cough parameters. After 21 day of OVA sensitization, cough parameters were significantly reduced, airway resistance after H inhalation was increased, and there were significant increases in IL-4, IL-5, and eosinophils in BALF. In conclusion, progress in asthmatic inflammation during 21-day OVA sensitization caused a gradual increase in inflammatory mediators, a decline in cough reflex, and enhanced bronchoconstriction. This experimental model of allergic asthma can be used for pharmacological modulations of defense reflexes and inflammation.
本研究旨在制备并评估变应性哮喘的实验模型。在卵清蛋白(OVA)致敏豚鼠,于第 0、7、14、21 天分别暴露后,研究咳嗽反射、支气管收缩和炎症程度的变化。在双室体描仪中,通过柠檬酸吸入诱导咳嗽反射。在体检查气道平滑肌对组胺(H)(10(-8)-10(-3)mol/L)的体外反应和对 H 雾化(10(-6)mol/L)的体内反应,评估气道平滑肌反应性。BALF 中的白细胞介素-4(IL-4)、白细胞介素-5(IL-5)和嗜酸性粒细胞计数用作气道炎症的参数。在 OVA 致敏 7 天后,体外累积浓度的 H 引起的气管平滑肌收缩性增加,咳嗽参数增加。在 OVA 致敏 14 天后,H 引起的气管平滑肌收缩性进一步增加,气道阻力增加,咳嗽参数略有增加。在 OVA 致敏 21 天后,咳嗽参数显著降低,H 吸入后气道阻力增加,BALF 中的 IL-4、IL-5 和嗜酸性粒细胞显著增加。总之,在 21 天 OVA 致敏期间哮喘炎症的进展导致炎症介质逐渐增加、咳嗽反射下降和支气管收缩增强。这种变应性哮喘的实验模型可用于防御反射和炎症的药理学调节。