生长因子在慢性阻塞性肺疾病大鼠模型气道重塑中的作用

目的　观察转化生长因子 (TGF) β1、表皮生长因子 (EGF)及碱性成纤维生长因子(bFGF)在慢性阻塞性肺疾病 (COPD)大鼠模型肺内表达与分布的变化 ,探讨其与气道重塑的关系及药物干预的影响。方法　两次气管内注入脂多糖及熏香烟法建立大鼠COPD模型 (B组 )。C组于制作模型后雾化吸入肝素溶液。D组于制作模型后静脉注射 2次TGF β1单抗。用图像分析系统检测支气管平滑肌及胶原厚度 ,用免疫组化及原位杂交法检测各生长因子蛋白和基因表达的相对含量。结果　与A组 (对照组 )相比 ,B组大鼠支气管平滑肌及胶原纤维显著增厚 (P <0 0 1) ,三种生长因子在支气管黏膜上皮、肺小动脉内皮和肺泡巨噬细胞的表达显著增强 (P <0 0 0 1～ 0 0 5 )。D组TGF β1较B组显著减少 (P <0 0 1) ,C组各生长因子有减少趋势。支气管上皮细胞三种生长因子与平滑肌厚度、TGF β1与胶原厚度、肺小动脉内皮细胞TGF β1及bFGF与平滑肌厚度之间均呈正相关 (P <0 0 5～0 0 1)。结论　TGF β1、EGF及bFGF在气道重塑和肺小动脉重建中可能起重要作用。

The potential role of growth factor in the airway wall remodeling of a chronic obstructive pulmonary disease rat model and the effects of drugs on them

OBJECTIVE: To evaluate the expression and distribution of transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) in the lung tissue of chronic obstructive pulmonary (COPD) rat models and the relationship between these growth factors and the airway wall remodeling. The effects of drugs on them were also investigated. METHODS: The COPD rat model (model group) was established by intratracheal instillation of lipopolysaccharide twice and daily exposure to cigarette smoking. Drug intervention groups received daily inhalation of heparin since the second week and TGF-beta1 monoclonal antibody (TB21) 0.5 mg twice through the tail veins. At the end of four weeks, the thickness of the smooth muscle and collagen in bronchi and pulmonary arterioles were measured by computer image analyzer, also the protein and gene relative content of these growth factors as well as the effects of drugs on them were observed. RESULTS: There was a significant increase in the smooth muscle and collagen thickness in the bronchi and pulmonary arterioles of the model group in comparison with that of the control group (P < 0.01), the relative contents for TGF-beta1, EGF and bFGF in the epithelial cells of the bronchi, endothelial cells of the pulmonary arterioles and alveolar macrophages of the model group were significantly higher than those of control group (P < 0.001 approximately 0.05). The relative content for TGF-beta1 in TB21 group was significantly lower than that of model group (P < 0.01). These were statistical positive relationships between the smooth muscle e thickness of bronchi and the relative contents for TGF-beta1, EGF and bFGF in the epithelial cells, between the collagen thickness of the bronchi and the relative content for TGF-beta1, between the smooth muscle thickness of the pulmonary arterioles and the relative content for TGF-beta1 and EGF in the endothelial cells (P < 0.05 approximately 0.01). CONCLUSION: TGF-beta1, EGF and bFGF may play an important role in the airway wall and pulmonary arteriole structure remodeling in COPD, the intervention against TGF-beta1 and long term inhalation of heparin mat be helpful for the inhibition of airway wall remodeling in human COPD and worth of further observation.