Kasahara D I, Perini A, Lopes F D T Q S, Arantes-Costa F M, Martins M A, Nunes M P T
Laboratório de Terapêutica Experimental, Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2005 May;38(5):723-30. doi: 10.1590/s0100-879x2005000500009. Epub 2005 May 25.
Beta-2-agonists have been widely used by asthmatic subjects to relieve their obstructive symptoms. However, there are reports that continuous use could lead to loss of bronchial protection and exacerbation of asthma symptoms. We evaluated the effect of two regimens of salbutamol administration (twice and five times a week) in a model of chronic airway inflammation in male Hartley guinea pigs (protocol starting weight: 286 +/- 30 g) induced by repeated exposures to aerosols of ovalbumin (OVA). After sensitization, guinea pigs were exposed to aerosols of 0.1 mg/ml salbutamol solution twice a week (OVA + S2x, N = 7) or five times a week (OVA + S5x, N = 8). We studied allergen-specific (OVA inhalation time) and -nonspecific (response to methacholine) respiratory system responsiveness. Seventy-two hours after the last OVA challenge, guinea pigs were anesthetized and tracheostomized, respiratory system resistance and elastance were measured and a dose-response curve to inhaled methacholine chloride was obtained. Specific IgG1 was also quantified by the passive cutaneous anaphylactic technique. OVA-sensitized guinea pigs (N = 8) showed reduction of the time of OVA exposure before the onset of respiratory distress, at the 5th, 6th and 7th exposures (P < 0.001). The OVA + S2x group (but not the OVA + S5x group) showed a significant increase in OVA inhalation time. There were no significant differences in pulmonary responsiveness to methacholine among the experimental groups. OVA + S2x (but not OVA + S5x) animals showed a decrease in the levels of IgG(1)-specific anaphylactic antibodies compared to the OVA group (P < 0.05). Our results suggest that, in this experimental model, frequent administration of beta(2)-agonists results in a loss of some of their protective effects against the allergen.
β2 激动剂已被哮喘患者广泛用于缓解其阻塞性症状。然而，有报道称持续使用可能导致支气管保护作用丧失和哮喘症状加重。我们在雄性 Hartley 豚鼠（初始体重：286±30 g）的慢性气道炎症模型中评估了两种沙丁胺醇给药方案（每周两次和每周五次）的效果，该模型由反复暴露于卵清蛋白（OVA）气雾剂诱导。致敏后，豚鼠每周两次（OVA + S2x，N = 7）或每周五次（OVA + S5x，N = 8）暴露于 0.1 mg/ml 沙丁胺醇溶液气雾剂。我们研究了变应原特异性（OVA 吸入时间）和非特异性（对乙酰甲胆碱的反应）呼吸系统反应性。在最后一次 OVA 激发后 72 小时，豚鼠麻醉并进行气管切开，测量呼吸系统阻力和弹性，并获得吸入氯化乙酰甲胆碱的剂量反应曲线。特异性 IgG1 也通过被动皮肤过敏技术进行定量。OVA 致敏的豚鼠（N = 8）在第 5、6 和 7 次暴露时，呼吸窘迫发作前的 OVA 暴露时间缩短（P < 0.001）。OVA + S2x 组（但不是 OVA + S5x 组）的 OVA 吸入时间显著增加。各实验组之间对乙酰甲胆碱的肺反应性无显著差异。与 OVA 组相比，OVA + S2x（但不是 OVA + S5x）动物的 IgG1 特异性过敏抗体水平降低（P < 0.05）。我们的结果表明，在这个实验模型中，频繁给予β2 激动剂会导致其对变应原的一些保护作用丧失。
