孟鲁司特对慢性阻塞性肺疾病大鼠气道炎症和重塑的影响及其机制

Effect and mechanism of montelukast on airway inflammation and remodeling in COPD rats

目的探讨孟鲁司特对慢阻肺大鼠气道炎症及重塑的作用及其影响气道重塑的机制。方法采用烟熏联合气管内注入脂多糖的方法建立大鼠慢阻肺模型(B组),对照组(A组)大鼠正常饲养,C组和D组大鼠分别在制作模型过程的最后2周给予孟鲁司特1mg/(kg·d)和孟鲁司特4mg/(kg·d)灌胃处理。实验结束后,收集支气管肺泡灌洗液(BALF)行细胞计数及分类。观察肺组织病理切片的气道炎症及重建情况,并行气道炎症评分及气道平滑肌厚度测定。免疫组化法检测大鼠肺组织碱性成纤维生长因子(b FGF)表达情况。结果与A组相比,B组大鼠BALF中白细胞总数及气道炎症评分明显增高,气道平滑肌显著增厚,b FGF表达水平显著增高(P<0.05)。C组和D组大鼠BALF中白细胞总数及气道炎症评分较B组降低,气道平滑肌增厚不如B组明显,b FGF表达水平较B组降低(P<0.05)。以上各项指标在C组和D组之间无明显差异(P>0.05)。b FGF的表达与支气管平滑肌厚度正相关(r=0.78,P<0.01)。结论孟鲁司特有抑制气道炎症及气道重塑的作用,其抑制气道重塑的机制与其抑制b FGF的表达有关。

Objective To investigate the effect of montelukast on airway inflammation and remodeling inCOPD rats and its mechanism of airway remodeling. Methods The COPDrat model （the by exposure to cigarette smoking and intratracheal instillation of lipopolysaccharide. The group A （the control group） was fed normally. The group Cand D were administered with montelukast 1 mg / （ kg · d） and montelukast 4 mg （kg ·d） respectively in the last 2 weeks of the model procedure. At the end of the experiment,the bronchoalveolar lavage fluid （ BALF） was collected and counted. The airway inflammation and reconstruction of lung tissue were observed. The airway inflammation score and airway smootli muscle thickness were measured. The expression of basicfibroblast growth factor （ bFGF） in lung tissue was detected by immunohistochemistry. Results Compared with thegroup A, the number of white blood cells and airway inflammation score in group B,the thickness of airway smooth muscle and the expression of bFGF B （P 〈 0. 05 ） . The airway inflammation score of the group C and the group Dwas lower thairway smooth muscle thickness was better than the group B. The expression of bFGF was lower in the group C and Dthan in the group B （ P〈 0. 05 ） . There was no significant diference between the C group and the D group in the a-bove indexes （ P〉 0. 05 ） . The expression of bFGF was positively correlated with the thickness of airway smooth muscle （ r = 0. 78 ,P 〈 0. 0 1 ） . Conclusion Montelukast can inhibit airway inflammation and airway remodeling. Themechanism of inhibition of airway remodeling is related with the inhibition of bFGF expression.