沙美特罗替卡松粉吸入剂对大鼠慢性阻塞性肺疾病气道重塑的影响

发布时间：2019-01-05 13:55

【摘要】：目的探讨不同剂量沙美特罗替卡松粉吸入剂(ICS/LABA)对大鼠慢性阻塞性肺疾病(COPD)气道重塑的干预作用。方法将40只Wistar大鼠随机分为对照组(A组)、模型组(B组)、低剂量ICS/LABA组(C组)、高剂量ICS/LABA组(D组)。采用烟熏加气管内注射脂多糖(LPS)法复制COPD模型,C、D组吸入中、高剂量ICS/LABA。观察肺功能和病理变化,肺泡灌洗液(BALF)中细胞计数和百分比,图像分析测量小气道平滑肌和管壁厚度,酶联免疫吸附(ELISA)法测定BALF中转化生长因子β1(TGF-β1)的表达,免疫组化法测定肺组织中基质金属蛋白酶9(MMP-9)、分泌性白细胞蛋白酶抑制剂(SLPI)的表达,实时荧光定量聚合酶链式反应(RT-PCR)检测肺组织中MMP-9mRNA的表达。结果 B组肺间质大量炎性细胞浸润,肺泡壁破坏,肺大疱形成,气管管壁和平滑肌增厚,C、D组有所减轻;B组TGF-β1、MMP-9水平与A组大鼠相比明显升高,SLPI则显著降低(P0.05);干预后C、D组TGF-β1、MMP-9水平与B组相比明显降低,而SLPI则明显升高(P0.05);D组TGF-β1、MMP-9阳性系数和mRNA相对含量[(82.06±4.43)(2.41±0.22)(6.156±8.86)]显著低于C组[(118.59±5.28)(3.09±0.28)(9.616±10.56)](P0.05),而SLPI(2.95±0.28)明显高于C组(2.11±0.26)(P0.05)。结论 ICS/LABA对COPD大鼠肺泡破坏及气道重塑有抑制作用,且高剂量优于低剂量,其机制可能与降低TGF-β1和MMP-9的表达及提高SLPI的水平有关。
[Abstract]:Objective to investigate the effects of different doses of salmeterol ticasone powder (ICS/LABA) on airway remodeling of (COPD) in rats with chronic obstructive pulmonary disease (COPD). Methods Forty Wistar rats were randomly divided into control group (group A), model group (group B), low dose ICS/LABA group (group C) and high dose ICS/LABA group (group D). The model of COPD was established by fumigation and intratracheal injection of lipopolysaccharide (LPS). In group C, high dose ICS/LABA. was inhaled. Lung function and pathological changes, cell count and percentage in alveolar lavage fluid (BALF), small airway smooth muscle and wall thickness were measured by image analysis, and the expression of transforming growth factor 尾 1 (TGF- 尾 1) in BALF was measured by enzyme linked immunosorbent assay (ELISA). The expression of matrix metalloproteinase-9 (MMP-9), secretory leukocyte protease inhibitor (SLPI) and real-time fluorescent quantitative polymerase chain reaction (RT-PCR) were detected by immunohistochemistry. Results in group B, the interstitial inflammatory cells were infiltrated, alveolar wall was destroyed, bullae was formed, tracheal wall and smooth muscle were thickened. Compared with group A, the level of TGF- 尾 1 MMP-9 in group B was significantly higher than that in group A (P0.05), the level of MMP-9 in TGF- 尾 1 in group C was significantly lower than that in group B (P0.05), and the level of MMP-9 in TGF- 尾 1 in group C was significantly higher than that in group B (P0.05). The positive coefficient of TGF- 尾 1 MMP-9 and the relative content of mRNA in group D [(82.06 卤4.43) (2.41 卤0.22) (6.156 卤8.86)] were significantly lower than those in group C [(118.59 卤5.28) (3.09 卤0.28) (9.616 卤10.56)] (P0.05). SLPI (2.95 卤0.28) was significantly higher than that in C group (2.11 卤0.26) (P0.05). Conclusion ICS/LABA can inhibit alveolar destruction and airway remodeling in COPD rats, and the high dose is superior to the low dose. The mechanism may be related to the decrease of the expression of TGF- 尾 1 and MMP-9 and the increase of SLPI level.
【作者单位】：泸州医学院附属医院呼吸一科;
【分类号】：R563.9

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