孟鲁司特对哮喘豚鼠气道嗜酸粒细胞炎症的抑制作用

目的　研究白三烯受体拮抗剂孟鲁司特 (mon telukast,MK )对哮喘豚鼠气道嗜酸性粒细胞 (Eosinophil,Eos)炎症的影响 ,探讨孟鲁司特拮抗哮喘气道炎症的可能机制。方法　以卵白蛋白致敏豚鼠制备哮喘模型。用密度梯度分离法分离并计数支气管肺泡灌洗液 (BALF)中不同密度的嗜酸性粒细胞 ;采用TUNEL技术原位检测嗜酸性粒细胞凋亡 ;通过ELISA法检测BALF中IL 5的含量 ;采用荧光酶标记法在PharmaciaUnicap 10 0System中测定BALF中嗜酸性粒细胞阳离子蛋白 (ECP)的水平。结果　孟鲁司特能降低哮喘豚鼠BALF中Eos的数量 ;在孟鲁司特治疗组 ,嗜酸性粒细胞凋亡指数明显升高 ,BALF中IL 5和ECP的含量降低 ,与模型组比较差异均有显著性。结论　降低气道IL 5和ECP的水平 ,促进嗜酸性粒细胞凋亡 ,减少嗜酸性粒细胞浸润 ,可能是白三烯受体拮抗剂孟鲁司特拮抗哮喘气道炎症的一个重要机制。

Inhibiting effect of montelukast on eosinophilic airway inflammation of asthmatic guinea pigs

Aim To study the effect of montelukast on eosinophilic airway inflammation of asthmatic guinea pigs,and explore possible mechanism of montelukast. Methods Experimental asthma model of guinea pigs was induced by ovalbumin in vivo. The eosinophils in BALF were separated by density gradient centrifugation. The apoptosis of eosinophils was labeled by TdT-mediated dUTP nick end labeling (TUNEL)technique. The content of IL-5 in BALF was detected by enzyme-linked immunosorbent assay (ELISA). The level of ECP in BALF was detected through fluorescence enzyme-labeled assay. Results In BALF of asthmatic guinea pigs model, the number of eosinophils and content of IL-5 and ECP increased obviously, while the apoptosis index of eosinophils was lowered. After treatment with montelukast, the number of eosinophils and content of IL-5 and ECP in BALF of asthmatic guinea pigs decreased significantly, while the apoptosis index of eosinophils was elevated significantly. Conclusion Montelukast can inhibit the eosinophilic airway inflammation of asthmatic guinea pigs. Lowering the levels of IL-5 and ECP in BALF, promoting apoptosis of eosinophils and relieving airway infiltration of eosinophils may be important mechanisms for montelukast to antagonize airway inflammation of asthma.