白三烯受体拮抗剂孟鲁斯特对小鼠气道炎症的抑制作用  

Inhibitory Effect of Cysteinyl Leukotriene Receptor Antagonist Montelukast on Mouse Airway Inflammation

作　　者：李雯[1] 夏金堂[2] 戚赐聪[3] 徐鸿绪[1] 邬扬源[3] 

机构地区：[1]中山大学附属第一医院普外科实验室,广东广州510080 [2]广州市第一人民医院外科,广东广州510180 [3]香港大学医学院内科实验室

出　　处：《中山大学学报（医学科学版）》2005年第6期659-663,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：中山大学"211"工程基金(2004-80000-0232101)

摘　　要：【目的】探讨白三烯受体1拮抗剂孟鲁斯特(montelukast，MK)抑制小鼠气道炎症的作用及可能的机制。【方法】致敏的BALB／c小鼠持续吸入10g／L雾化卵白蛋白(OVA)30min，OVA吸入前2d开始连续3d或5d尾静脉给予MK或生理盐水(saline)，OVA吸入后24h及72h取材，瑞氏染色观察支气管肺泡灌洗液(bronchoalveolar lavage fluid，BALF)中炎症细胞的渗出情况；ELISA方法检测血清、BALF和肺组织中有关细胞因子水平；HE、刚果红染色观察肺组织炎症细胞的渗出；免疫组化染色观察血管内皮细胞黏附分子-1(VCAM-1)和嗜酸性粒细胞趋化因子(eotaxin)的表达；原位杂交研究IL-5 mRNA的变化。【结果】给予MK5d减少BALF嗜酸性粒细胞渗出达90％以上，嗜酸性粒细胞减少随MK剂量(10、25、62.5mg／kg)的增加呈量效关系。ELISA结果表明给予3d MK使肺、血清和BALF中IL-5、IL-4水平显著降低，肺IL-13含量也明显减少(P＜0.05)。但MK组肺组织eotaxin下降与saline组比较无明显差异(P＞0.05)。免疫组化显示MK组肺组织VCAM-1和eotaxin表达比saline组明显减弱；原位杂交可见MK组肺组织IL-5 mRNA的表达比saline组减弱。【结论】MK减轻气道炎症，可能通过抑制VCAM-1表达和IL-5、IL-4、IL-13等细胞因子分泌起作用。急性哮喘中应用大剂量MK抗炎治疗值得进一步探讨。[Objective] To explore the effect and mechanism of montelukast （MK）, a selective cysteinyl leukotriene receptor 1 antagonist, on mouse airway inflammation. [Methods] Sensitized BALB/c mice were challenged with 10 g/L ovalbumin （OVA） for 30 min, MK or saline were intravenously given for 3 or 5 days from the second day before OVA challenge. Samples were collected at 24 h or 72 h after OVA challenge. Cellular infiltration of bronchoalveolar larvage fluid （BALF） was assessed by Wright stain. Cytokines expression levels in the lung, BALF, and serum were determined by enzyme-linked immunosorbent assay （ELISA）. Cellular infiltration in lung tissue was observed with HE and Congo Red stain. Expressions of VCAM-1 and eotaxin were observed by immunocytochemistry. IL-5 mRNA was investigated by in situ hybridization. [Results] MK administration for 5 days reduced the number of eosinophils by more than 90%. Reduction of eosinophils number was dependent on the doses of MK （10, 25, and 62,5 mg/kg）. MK given for 3 days significantly reduced the IL-5 and IL-4 levels in lung and serum as well as lung IL-13 level （P〈 0.05）, but there was no significant reduction of eotaxin in lung tissue compared with saline group （P 〉 0.05）. The expressions of VCAM-1, eotaxin, and IL-5 mRNA in lung tissue of MK treatment group were obviously lower compared with those of saline treatment group.[Conclusion] MK suppress airway inflammation by inhibiting the expression of VCAM-1 and production of IL-5, IL-4, and IL-13. The use of high dose of MK in acute asthma is worth of further stuty.

关 键 词：白三烯受体1拮抗剂MK 小鼠气道炎症 血管内皮细胞黏附分子 炎症细胞因子 

分 类 号：R581[医药卫生—内分泌]