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目的观察尿激酶型纤溶酶原激活物(u-PA)抑制剂氨氯吡咪对大鼠慢性阻塞性肺疾病(COPD)模型病理及病理生理改变的影响,探讨 u-PA 系统成分在 COPD 发病中的作用。方法健康 Wistar 大鼠24只随机分为3组:正常对照组、模型组和氨氯吡咪组。7周后检测各组大鼠的肺功能,支气管肺泡灌洗液(BALF)细胞计数及分类,天狼猩红染色观察支气管肺组织的胶原沉积,免疫组化染色观察 u-PA、u-PA 受体、纤溶酶原激活物抑制物1(PAI-1)的蛋白定位和表达。结果模型组大鼠的呼气阻力显著高于对照组和氨氯吡咪组,0.3 s 用力呼气容积/用力肺活量、呼气峰流速均显著低于对照组和氨氯吡咪组;模型组大鼠的 BALF 中白细胞总数、中性粒细胞、单核细胞和巨噬细胞构成比显著高于对照组和氨氯吡咪组;模型组大鼠以Ⅰ型胶原为主的细胞外基质在气道壁过度沉积,胶原面积显著高于对照组和氨氯吡咪组;模型组大鼠支气管肺组织 u-PA、u-PA 受体和 PAI-1蛋白表达的平均吸光度值[(0.166±0.010)、(0.158±0.024)和(0.171±0.012)]显著高于对照组[(0.137±0.015)、(0.122±0.009)和(0.144±0.005)]及氨氯吡咪组[(0.126±0.004)、(0.120±0.010)和(0.122±0.004)],且 u-PA 受体蛋白表达与中性粒细胞构成比呈显著正相关。结论应用 u-PA 抑制剂氨氯吡咪可显著减轻 COPD 大鼠的气道炎症和病理结构改变,u-PA 系统成分是 COPD 气道炎症和组织重塑环节中具有关联作用的重要物质。
Objective To investigate the effects of amikacin, a urokinase-type plasminogen activator (u-PA) inhibitor, on the pathology and pathophysiology of chronic obstructive pulmonary disease (COPD) in rats and to explore the role of u-PA system in COPD The role of the disease. Methods Twenty-four healthy Wistar rats were randomly divided into three groups: normal control group, model group and amiloride group. After 7 weeks, lung function, bronchoalveolar lavage fluid (BALF) cell count and classification were detected in each group, collagen deposition in bronchial lung tissue was observed by Sirius red staining and immunohistochemical staining was used to observe u-PA and u-PA Body, plasminogen activator inhibitor 1 (PAI-1) protein localization and expression. Results The expiratory resistance of rats in the model group was significantly higher than that in the control group and the amiloride group. The forced expiratory volume / forced vital capacity at 0.3 s and peak expiratory flow rate were significantly lower than those in the control group and the amiloride group The ratio of total white blood cells, neutrophils, monocytes and macrophages in BALF of rats was significantly higher than that of control group and amiloride group. In model group, type I collagen-based extracellular matrix The excessive wall deposition and collagen area were significantly higher in the model group than those in the control group and the amiloride group. The average absorbance values of u-PA, u-PA and PAI-1 in bronchial lung tissue in model group [(0.166 ± 0.010 ), (0.158 ± 0.024) and (0.171 ± 0.012)] were significantly higher than those in the control group [(0.137 ± 0.015), (0.122 ± 0.009) and (0.144 ± 0.005) , (0.120 ± 0.010) and (0.122 ± 0.004)], respectively, and the expression of u-PA receptor protein was positively correlated with the neutrophil constituent ratio. Conclusion The application of amlopidine, a u-PA inhibitor, can significantly reduce the airway inflammation and pathological changes in COPD rats. The u-PA system is an important substance that plays an important role in COPD airway inflammation and tissue remodeling.