半胱氨酰白三烯 1/2 受体双重拮抗剂对豚鼠哮喘模型中变应原诱导的气道高反应性和气道炎症的影响。

Effects of a cysteinyl leukotriene dual 1/2 receptor antagonist on antigen-induced airway hypersensitivity and airway inflammation in a guinea pig asthma model.

机构信息

Department of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, Japan.

出版信息

Int Arch Allergy Immunol. 2011;155 Suppl 1:90-5. doi: 10.1159/000327439. Epub 2011 Jun 1.

DOI:10.1159/000327439

PMID:21646802

Abstract

BACKGROUND

Little is known about the role of the cysteinyl leukotriene (cysLT) 2 receptor in the pathophysiology of asthma. The aim of this study is to investigate the effects of a cysLT1 receptor antagonist (montelukast) and a dual cysLT1/2 receptor antagonist (BAY-u9773) on airway hypersensitivity and airway inflammation induced by antigen challenge in ovalbumin (OVA)-sensitized guinea pigs.

METHODS

Male Hartley guinea pigs sensitized with OVA were intraperitoneally administered 0.1, 1, or 10 mg/kg of montelukast or 0.1 mg/kg of BAY-u9773 and then challenged with inhaled OVA. Airway reactivity to acetylcholine, inflammatory cells in bronchoalveolar lavage (BAL) fluid, and eosinophil infiltration in airway walls after OVA challenge were evaluated.

RESULTS

Pretreatment with 1 or 10 mg/kg, but not 0.1 mg/kg, of montelukast significantly suppressed airway hypersensitivity and eosinophil infiltration into the BAL fluid. Moreover, 0.1 mg/kg of BAY-u9773 significantly suppressed the development of these markers. The suppressive effects of BAY-u9773, although not significantly different, trended toward being greater than those of montelukast. Although all of the doses of montelukast tested and 0.1 mg/kg of BAY-u9773 significantly suppressed eosinophil infiltration in airway walls, the suppressive effect of BAY-u9773 was significantly greater than that of 0.1 mg/kg of montelukast.

CONCLUSION

Signaling may contribute to the pathophysiology of asthma via the cysLT1/2 receptor.

摘要

背景

关于半胱氨酰白三烯（cysLT）2 受体在哮喘病理生理学中的作用知之甚少。本研究旨在探讨半胱氨酰白三烯 1 受体拮抗剂（孟鲁司特）和双重半胱氨酰白三烯 1/2 受体拮抗剂（BAY-u9773）对卵清蛋白（OVA）致敏豚鼠抗原激发后气道高反应性和气道炎症的影响。

方法

用 OVA 致敏雄性 Hartley 豚鼠，腹腔内给予 0.1、1 或 10 mg/kg 的孟鲁司特或 0.1 mg/kg 的 BAY-u9773，然后用吸入 OVA 进行挑战。评估乙酰胆碱诱导的气道反应性、支气管肺泡灌洗液（BAL）中的炎症细胞和 OVA 激发后气道壁中的嗜酸性粒细胞浸润。

结果

1 或 10 mg/kg，但不是 0.1 mg/kg 的孟鲁司特预处理显著抑制气道高反应性和 BAL 液中的嗜酸性粒细胞浸润。此外，0.1 mg/kg 的 BAY-u9773 显著抑制这些标志物的发展。BAY-u9773 的抑制作用虽然没有显著差异，但趋势上大于孟鲁司特。尽管测试的所有剂量的孟鲁司特和 0.1 mg/kg 的 BAY-u9773 均显著抑制气道壁中的嗜酸性粒细胞浸润，但 BAY-u9773 的抑制作用明显大于 0.1 mg/kg 的孟鲁司特。