摘要
目的 :研究白三烯受体拮抗剂对哮喘气道炎症过程及肺内一氧化氮合酶 (NOS)的影响。方法 :C57BL/6J小鼠分为 3组 :哮喘组 (7只 ) ,正常对照组 (6只 ) ,扎鲁司特 (白三烯受体拮抗剂 )组 (7只 )。建立小鼠哮喘模型 ,给予口服扎鲁司特 40mg·kg 1 ·d 1 ,共 5d ,观察支气管肺泡灌洗液 (BALF)中白细胞总数 ,嗜酸细胞百分比 (EOS % ) ,血涂片 ,骨髓片中EOS % ,并用免疫组化的方法观察使用扎鲁司特后诱生型一氧化氮合酶 (iNOS)、内皮型一氧化氮合酶 (eNOS)的表达情况。结果 :哮喘组BALF中白细胞总数 [(1 3 .9± 0 .8)× 1 0 6 ml 1 ]、EOS % [(47.75± 1 3 .0 9) % ]显著高于正常对照组 (P <0 .0 0 1 ) ,正常对照组相应数值分别为 (1 .9± 0 .5)× 1 0 6 ml 1 和 (0 .2± 0 .0 1 ) % ,口服扎鲁司特后BALF中白细胞总数 [(1 .3± 0 .4)× 1 0 6 ml 1 ]、EOS % [(1 .33± 1 .0 7) % ]显著低于哮喘组 (P <0 .0 0 1 ) ,哮喘组激发后第一天血涂片中EOS % [(1 8.75± 8.54) % ]显著高于对照组 [(1 .5± 1 .0 ) % ,P <0 .0 0 1 ] ,扎鲁司特组在激发后第 1天血涂片中EOS %则较正常对照组明显下降 [(6 .95± 3 .83) % ] ,哮喘组骨髓片中EOS % [(1 3 .5±3 .9) % ]显著高于正常对照组 [(2 .5± 2 .9) % ] ,而扎鲁司特组 [(
Objective:To investigate the role of Zafirlukast, a selective leukotriene D 4 receptor antagonist in treatment of asthmatic inflammation and its effect in the expression of nitric oxide synthase (NOS) in lungs. Methods:A murine model was set up(asthma model group,control mice group ),then the number of WBC,eosinophils %(EOS%) in bronchoalveolar lavage fluid (BALF),eosinophils% (EOS%) in blood and bone marrow were measured after treatment with Zafrilukast. The expression of inducible nitric oxide synthase (iNOS) and of endothelium nitric oxide synthase (eNOS) were studied by immunohistochemistry. Results:There was a significant increase in number in WBC [(13.9±0.8)×10 6 ml 1 vs (1.9±0.5) ×10 6 ml 1 , P <0.001], EOS%[(47.75± 13.09)% vs (0.2±0.01)%, P <0.001] in BALF after antigen challenge.There was also a significant increase in EOS% of the first day after challenge in blood[(18.75±8.54)% vs (1.5±1.0)%, P <0.001] and EOS% in bone marrow[(13.5±3.9)% vs (2.5±2.9)%, P <0.001].After administration of Zafrilukast the number of WBC [ (1.3±0.4)×10 6/ml, P <0.001], EOS% [ (1.33± 1.07)%, P <0.001], EOS% of the first day after challenge in blood [(6.95±3.83)%, P <0.001]were significantly decreased. But there was no significant reduction in bone marrow after management with Zafrilukast .There was a significant reduction of iNOS expression , but no siginificant change in eNOS expression after treatment with Zafrilukast. Conclusion: EOS in asthmatic inflammation originate from the margin pool of blood and the bone marrow. Zafrilukast can inhibit EOS infiltration in asthmatic inflammation, and can also inbibit iNOS expression in lungs directly or indirectly.
出处
《北京大学学报(医学版)》
CAS
CSCD
北大核心
2002年第1期52-56,共5页
Journal of Peking University:Health Sciences