噻托溴铵在COPD大鼠气道炎症中的作用  

Effects of Tiotropium Bromide on Airway Inflammation in a Rat Model with COPD

作　　者：何牡丹[1] 荣令[1] 周新[1] 

机构地区：[1]上海交通大学附属第一人民医院呼吸科,上海200080

出　　处：《中国呼吸与危重监护杂志》2009年第3期212-215,共4页Chinese Journal of Respiratory and Critical Care Medicine

摘　　要：目的探讨噻托溴铵对COPD气道炎症和气道阻力的影响。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1d和第14d气管内滴入脂多糖200μg,每日烟熏(第1d和第14d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雾化吸入噻托溴铵(生理盐水溶解,0.12mmol/L,10min)共28d。大鼠处死前行肺功能测定;取左肺BALF进行细胞分类计数;肺组织HE染色行病理学评价;ELISA法测定BALF及血清IL-8和白三烯B4(LTB4)浓度。结果①模型组大鼠的气道阻力显著高于正常对照组,顺应性明显降低(P<0.01);治疗组大鼠气道阻力较模型组明显降低(P<0.01),顺应性明显增加(P<0.05)。②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。③模型组BALF中细胞总数、中性粒细胞比例明显升高;治疗组细胞总数、中性粒细胞比例较模型组明显降低。④模型组血清及BALF中IL-8和LTB4浓度均较正常对照组明显升高(P<0.01),治疗组与模型组比较IL-8和LTB4水平显著降低(P<0.01)。结论噻托溴铵可以减轻COPD大鼠的气道炎症,延缓肺功能恶化,这一作用可能是通过抑制炎症介质的释放来实现的。Objective To investigate the effects of Tiotropium Bromide on airway inflammation in a rat model of chronic obstructive pulmonary disease （ COPD ）. Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS（200 μg,intratraehcally injected at the 1^st and the 14^th day） and tobacco exposure（from the 2^nd day to the 30^th day except the 14th day） to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide （0.12 mmol/L, 10 minutes ） 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 concentrations of IL-8 and LTB4 , total and differential cells counts in bronehoalveolar lavage fluid（BALF） were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.

关 键 词：慢性阻塞性肺疾病 噻托溴铵 气道炎症 气道阻力 白细胞介素8 白三烯B4 

分 类 号：R563.9[医药卫生—呼吸系统]