Couëtil Laurent L, Art Tatiana, de Moffarts Brieuc, Becker Martine, Mélotte Dorothée, Jaspar Fabrice, Bureau Fabrice, Lekeux Pierre
Department of Physiology, Faculty of Veterinary Medicine, University of Liège, Belgium.
J Vet Intern Med. 2006 Mar-Apr;20(2):399-406. doi: 10.1892/0891-6640(2006)20[399:eobdad]2.0.co;2.
Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kappaB and AP-1 in bronchial cells of RAO-affected horses. Seven horses with RAO were exposed to moldy hay until they developed airway obstruction on 3 separate occasions. In a crossover design, they were then treated with a placebo (injection on day 1), inhaled beclomethasone (500 microg q12h for 10 days), or dexamethasone (0.06 mg/kg, IM on day 1) and monitored for 10 days. Pulmonary function, bronchoalveolar lavage fluid cytology, and NF-kappaB and AP-1 activity in bronchial brushing cells were measured before (day 1) and after treatment (day 10). Treatment with beclomethasone resulted in significantly improved pulmonary function of RAO-affected horses compared with placebo and dexamethasone treatments. However, none of the treatments had an effect on bronchoalveolar lavage fluid cytology or NF-kappaB and AP-1 activity. These findings reveal that, in a model of severe RAO, the benefits of low-dose inhaled beclomethasone on pulmonary function are not accompanied by a decrease in airway inflammatory cells or a suppression of transcription factors NF-kappaB and AP-1 DNA-binding activity.
糖皮质激素(GC)疗法被认为对治疗马的复发性气道阻塞(RAO)有效。GC的抗炎特性被认为是通过抑制转录因子如核因子-κB(NF-κB)和活化蛋白-1(AP-1)来抑制炎症基因表达介导的。本研究的目的是评估低剂量吸入丙酸倍氯米松和注射地塞米松21-异烟酸盐对受RAO影响的马的临床症状、肺功能、气道细胞学以及支气管细胞中NF-κB和AP-1活性的影响。七匹患有RAO的马暴露于发霉干草中,直到它们在3个不同场合出现气道阻塞。在交叉设计中,然后它们接受安慰剂治疗(第1天注射)、吸入倍氯米松(500微克,每12小时一次,共10天)或地塞米松(0.06毫克/千克,第1天肌肉注射),并监测10天。在治疗前(第1天)和治疗后(第10天)测量肺功能、支气管肺泡灌洗液体细胞学以及支气管刷检细胞中的NF-κB和AP-1活性。与安慰剂和地塞米松治疗相比,倍氯米松治疗使受RAO影响的马的肺功能显著改善。然而,所有治疗对支气管肺泡灌洗液体细胞学或NF-κB和AP-1活性均无影响。这些发现表明,在严重RAO模型中,低剂量吸入倍氯米松对肺功能的益处并未伴随着气道炎症细胞的减少或转录因子NF-κB和AP-1 DNA结合活性的抑制。