摘要
目的:观察COPD大鼠模型气道重塑的特点及其在肺功能损害中的作用,探讨不同药物干预对气道重塑的影响。方法:用两次气管内注入脂多糖(LPS)及熏香烟的复合刺激法建立大鼠COPD模型(模型组),转化生长因子-β_1(TGF-β_1)单抗组于制作模型第6、19天经尾静脉注射TGF-β_1单抗各0.5mg。其他各药物干预组于制作模型第8天起分别雾化吸入布地奈得(普米克组)、溴化异丙托品(爱喘乐组)和肝素(肝素组)溶液。4周后检测肺病理切片小支气管平滑肌及胶原厚度,用放免法检测血清和BALF中细胞外基质(ECM)成分PCⅢ、Ln及HA,以及药物干预对以上指标的影响。结果:模型组小支气管平滑肌及胶原纤维较对照组显著增厚,其厚度均与通气功能指标"FEV_(0.3)"呈显著负相关,TGF-β_1单抗组小支气管胶原增生显著减少,肝素组平滑肌厚度显著减少。COPD患者血清和大鼠模型血清、BALF中PCⅢ、Ln及HA均较对照组有不同程度增高。各药物干预组PCⅢ、Ln及HA较模型组有不同程度降低。结论:模型组小支气管平滑肌及胶原纤维显著增厚,构成气道重塑的主要病理基础;针对TGF-β_1等生长因子进行干预、长期雾吸肝素,有可能为COPD气道重塑的防治提供线索。ECM过度沉积是COPD的重要特点,布地奈德、TGF-β_1单抗、异丙托品及肝素的干预能减轻Ln增殖。
Objective: To study the pathological features of the smooth muscle and collagen in bronchi of the COPD rat models and their roles in the airway obstruction, to measure the levels of PCⅢ、Ln and HA in peripheral blood and BALF of COPD rat models and in blood of COPD patients, respectively, and to observe effects of different drugs on the above parameters. Methods:The rat COPD model (model group)was established by intratracheal instillation of lipopolysaccharide (LPS 200 μg/200μL) twice and daily exposure to cigarette smoke. Drug intervention groups received daily inhalation of budesonide, atrovent and heparin respectively beginning from the second week and TGF-β_1. monoclonal antibody(TB21)0.5mg twice through the tail veins. At the end of four weeks, the thickness of the smooth muscle and collagen in bronchi and pulmonary arteriole were measured by means of image analyzer (CMIAS), the levels of PCⅢ、Ln and HA were determined by using the RIA method. Results:Significant thickness of the smooth muscle and collagen was seen in the bronchi and pulmonary arterioles of model group in comparison with that of the control group, TB21 group and heparin group showed significant decrease in the thickness of the collagen and smooth muscle in the bronchi , respectively, and there were statistical negative relationships between the thickness of both smooth muscle, collagen in the bronchi and FEV_(0.3). The levels of PCⅢ、Ln and HA in COPD patients and COPD rat models were significantly higher than those of control groups. The above parameters were reduced in different degrees in drug intervention groups. Especially, heparin could significantly decrease the smooth muscle thickness and TB21 decrease the collagen thickness. Conclusion: The significant thickening of smooth muscle and collagen in the bronchi of the rat COPD model may be the most important pathological basis for airway wall remodeling. The intervention against TGF-β, and long term inhalation of heparin might be helpful for the inhibition of airway remodeling in COPD patients and worth of further observation. The excessive depositions of ECM are important characteristics of COPD ,and the intervention with budesonide、TB21、atrovent and heparin may decrease the release of Ln.
出处
《感染．炎症．修复》
2000年第1期51-55,共5页
Infection Inflammation Repair
