探讨沙美特罗／丙酸氟替卡松在COPD大鼠气道炎症中的作用

Effects of shah mette Io/fluticasone propionate on airway inflammation in a rat model with COPD

目的探讨沙美特罗（50μg）／丙酸氟替卡松（250μg）对COPD气道炎症的影响。方法30只大鼠随机分为3组，每组10只。正常对照组：正常饲养28d；模型组：第1天和第14天气管内滴入脂多糖200μg，每日烟熏（第1天和第14天除外），共28d；治疗组：与模型组相同的方法建立COPD模型，并于每日烟熏前30min雾化吸入沙美特罗（50ug）／rg酸氟替卡松（250μg），共28d。大鼠处死前行肺功能测定；肺组织HE染色行病理学评价；取左肺BALF进行细胞分类计数；ELISA法测定BALF及血清中IL-8、肿瘤坏死因子α（TNF—α）和基质金属蛋白酶9（MMP-9）的浓度。结果模型组大鼠的气道阻力显著高于正常对照组（z=2．72，P〈0．05），肺动态顺应性显著降低（z=-1．97，P〈O．05）；与模型组相比，治疗组的气道阻力显著降低（z=-2．42，P〈0．05），肺动态顺应性显著升高（z=-2．19，P〈0．05）。病理检查显示模型组气道炎症加重，且出现明显肺气肿；治疗组也出现了炎症和肺气肿，但程度较轻。模型组BALF中细胞总数、中性粒细胞、巨噬细胞数较正常对照组显著升高（z=3．79，3．79，3．78，P〈0．05）；治疗组细胞总数、中性粒细胞、巨噬细胞数较模型组显著降低（z=-3．78，-3．78，-3．78，P〈0．05）。与正常对照组比较，模型组血清及BALF中IL-8、TNF—d均显著升高（t-3．72，3．33，5．01，2．45，P〈0．05），血清与BALF中的MMP-9也显著升高（z=2．04，2．50，P值均〈0．05）。治疗组与模型组比较，血清与BALF中的IL8、TNF—α浓度均显著下降（t=-3．54，-2．64，-4．11，-2．64，P值均〈0．05），血清与BALF中的MMP-9也显著下降（z=-2．27，-2．38，P值均〈0．05）。结论沙美特罗（50μg）／丙酸氟替卡松（250μg）通过抑制炎性细胞的活化及某些炎性介质的释放减轻COPD气道炎症，并且能抑制MMP-9进而阻止气道重塑。

Objective To investigate the effects of mette lo （50 μg）/fluticasone propionate （250 μg） on airway inflammation in a rat model with chronic obstructive pulmonary disease（COPD）. Methods Thirty rats were randomly divided into three groups. Group A received normal breeding as controls. Group B and group C received LPS （200 μg,intratracheally injected at the 1^st and the 14^th day） and tobacco exposure （from the 2^nd day to the 28^th day except the 14^th day） to establish COPD model,and group C received a nebulized dose of mette Io （50 μg）/fluticasone propionate （250 μg） 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The differential cells counts in bronchoalveolar lavage fluid （BALF） were examined. The concentrations of IL-8, TNF-α and MMP-9 in blood and BALF were determined by ELISA. Results Airway resistance significantly increased （ z =-2.72, P〈0.05） and pulmonary dynamic compliance significantly reduced （ z = -1.97, P 〈0.05） in rats in the group B compared with those in the group A,and airway resistance significantly reduced（ z = -2.42, P 〈0.05） and pulmonary dynamic compliance significantly increased（ z =2.19, P 〈0.05） in rats in the group C compared with those in the group B （ P 〈0.05）. Severe lung inflammation and emphysema were demonstrated in rats in group B,and the pathological changes in rats in group C were mild. The total cell, neutrophils and macrophage in BALF were significantly higher in group B than those in group A （ z = 3.79,3.79,3.78, P 〈0. 05）, and the inflammatory cells in BALF were significantly lower in group C than those in group B （ z =-3.78,-3.78,-3.78, P d0.05）. The level of IL-8,TNF-α in serum and BALF （t=3.72,3.33,5.01,2.45, P〈0.05） and MMP-9 in serum and BALF （z =2.04,2.50, P 〈0.05） were significantly higher in group B than those in group A, and the level of IL-8, TNF-α in serum and BALF （t =-3.54,-2.64,-4. 11,-2.64, P 〈0.05） and MMP-9 in serum and BALF（-2.27, -2.38, P〈 0.05） were significantly lower in group C than those in group B. Conclusions Mette lo （50 μg）/ fluticasone propionate （250 μg） can alleviate the lung inflammation by inhibiting the activities of inflammatory ceils and release of inflammatory mediators, and can prevent airway remodeling by inhibiting MMP-9.