Sorkness R, Lemanske R F
School of Pharmacy, University of Wisconsin-Madison 53792-3244, USA.
Pulm Pharmacol. 1996 Aug;9(4):219-22. doi: 10.1006/pulp.1996.0027.
Respiratory viral infections have been associated with exacerbations of asthma in humans, and are known to produce airway obstruction and hyperresponsiveness in rats. Virus-induced airway dysfunction may result in part from inflammatory cells and their products, and agents that target these mechanisms might therefore attenuate viral airway injury. The 21-aminosteroid class of drugs has been reported to attenuate tissue injury in a variety of models, and we hypothesized that U-83836E, an orally-active aminosteroid, would prevent the development of airway dysfunction during acute viral illness. Adult rats were inoculated with either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated rats were placed in a body plethysmograph for measurements of airway obstruction (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to i.v. methacholine; lungs were lavaged to obtain inflammatory cells. The water-treated virus group was significantly different from the non-infected controls for all variables. Virus-induced hyperresponsiveness was attenuated (P = 0.027) by aminosteroid treatment, although airway obstruction and inflammation were not improved by the treatment. We conclude that 21-aminosteroids may protect airways from virus-induced hyperresponsiveness.
呼吸道病毒感染与人类哮喘发作有关，并且已知会在大鼠中导致气道阻塞和高反应性。病毒诱导的气道功能障碍可能部分源于炎症细胞及其产物，因此靶向这些机制的药物可能会减轻病毒性气道损伤。据报道，21-氨基类固醇类药物在多种模型中可减轻组织损伤，我们推测口服活性氨基类固醇U-83836E可预防急性病毒感染期间气道功能障碍的发生。成年大鼠接种1型副流感（仙台）病毒或无菌载体，每天通过口服灌胃给予20 mg/kg U-83836E或水两次，并在接种后第5、6或7天进行研究。将麻醉、麻痹、机械通气的大鼠置于体容积描记仪中测量气道阻塞（阻力、动态顺应性、正常碳酸血症时的PaO2）以及对静脉注射乙酰甲胆碱的反应性；对肺进行灌洗以获取炎症细胞。水处理病毒组在所有变量上与未感染对照组均有显著差异。氨基类固醇治疗可减轻病毒诱导的高反应性（P = 0.027），尽管该治疗并未改善气道阻塞和炎症。我们得出结论，21-氨基类固醇可能保护气道免受病毒诱导的高反应性影响。
