摘要
目的:探讨噻托溴铵对慢性阻塞性肺疾病(COPD)病理过程和呼吸功能的影响。方法:30只大鼠随机分为3组,每组l0只。空白对照组(A组):正常饲养12周;模型组(B组):第1天,第14天和29天气管内滴入200μg(200μL)生理盐水脂多糖(LPS),每天烟熏(滴脂多糖当天除外),共12周;治疗组(C组):与模型组相同的方法建立COPD模型,并于第29天后在烟熏前30 min介入雾化吸人噻托溴铵(生理盐水溶解,0.12 mmoL.L-1,20 min,60 nmol/只)共12周。大鼠处死前行肺功能测定;取左肺BALF进行细胞分类计数;取右侧中叶肺组织HE染色行病理学评价;ELISA法测定BALF及血清白介素-6(IL-6)和白三烯C4(LTC4)浓度。结果:①与正常组比较,烟熏4周后造模组体重明显下降(P<0.05);与模型组比较,噻托溴胺介入治疗后2周后即第8周体重增加(P<0.05)。②与空白对照组比较,模型组大鼠的气道阻力显著升高(P<0.01),肺顺应性显著降低(P<0.01),0.2 s呼气量(FEV0.2)/最大肺活量(FVC)与呼吸峰流速(PEF)显著下降(P<0.05)。噻托溴铵组气道阻力较模型组明显降低(P<0.05),仍显著高于空白对照组(P<0.05);顺应性较模型组显著升高(P<0.05),FEV0.2/FVC(%)显著下降(P<0.05),与空白对照组比较无显著差异,PEF显著下降(P<0.05),但未回复到正常组水平(P<0.05)。③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。④与空白对照组比较,模型组BALF中细胞总数、单核巨噬细胞数、中性粒细胞数、淋巴细胞数均明显升高(P均<0.01)。噻托溴铵组BALF中细胞总数、单核巨噬细胞数、中性粒细胞数较模型组显著下降(P均<0.01)。⑤模型组血清及BALF中IL-8和LTC4浓度均较空白对照组明显升高(P<0.05),治疗组与模型组比较IL-6和LTC4水平显著降低(P<0.01)。结论:噻托溴铵不但能通过阻断毒覃碱型乙酰胆碱受体来够松弛呼吸道平滑肌改善肺功能,还可能是通过抑制炎症介质的
Objective：The purpose of this experiment is to investigate the impact of tiotropium on the pathological process of chronic obstructive pulmonary disease （COPD） and respiratory function. Method： Wistar rats were randomized into three groups：normal control group（group A）,COPD group（group B）,tiotropium bromide treated group（group C）.The COPD rat model was constructed by intratracheal instillation of 200 μg lipopolysaccharide three times and daily exposure to cigarette smoking,in 12 weeks. Histological examination on the right side of the mid-lung tissue was performed with Hematoxylin-Eosin staining.The concentrations of IL-6 and LTC4,total and differential cells counts in bronchoalveolar lavage fluid（BALF）were examined,and the concentrations of IL-6 and LTC4 in blood surem were also examined by ELISA. Result： Severe lung inflammation and decreased lung function were demonstrated in the group B compared with those in the group A.The inflammatory cell counts in BALF,and the levels of IL-6 and LTC4 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.①The body weight decreased significantly after four weeks in the group B compared with the group A （P〈0.05）; Compared with the group B, thiophene care bromide interventional treatment after two weeks the body weight was gained （P〈0.05）. ② Respiratory function was significantly deteriorated in the group B compared with those in the group A.Tiotropium repair improved compared with the group B. ③ lung inflammation and emphysema were demonstrated in the group B compared with those in the group A.The group C also appeared inflammation and emphysema, but to a lesser extent. ④ The inflammatory cell counts in BALF,and the levels of IL-6 and LTC4 in BALF and serum were significantly increased in the group B compared with those in the group A（P〈0.05）.Tiotropium bromide administration improved the above parameters （P〈0.
出处
《中国实验方剂学杂志》
CAS
北大核心
2013年第5期190-194,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家科技重大专项"重大新药创制"课题(2009ZX09301-001)
上海市教育委员会预算内科研项目(2010JW52)
