摘要
目的 观察慢性阻塞性肺疾病 (COPD)大鼠模型气道重塑的特点及在肺功能损害中的作用 ,探讨转化生长因子β1(TGF β1)、表皮生长因子 (EGF)及碱性成纤维细胞生长因子 (b FGF)与气道重塑的关系及不同药物干预的影响。方法 两次气管内注入脂多糖 (LPS)及每日熏香烟的复合刺激法建立大鼠COPD模型 (模型组 ) 12只 ,TGF β1单抗组 6只于制作模型后第 6、19d经尾静脉注射TGF β1单抗各 0 5mg。其它各药物干预组于制作模型第 8d起分别雾化吸入布地奈德 (布地奈德组 ,12只 )、溴化异丙托品 (溴化异丙托品组 ,12只 )和肝素 (肝素组 ,6只 )溶液。 4周后检测小支气管平滑肌及胶原厚度 ,用免疫组化法及原位杂交法观察各生长因子在支气管肺内的表达 ,用放免法检测血清和BALF中细胞外基质 (ECM)成分Ⅲ型前胶原 (PCⅢ )、层粘连蛋白 (Ln)及透明质酸 (HA)。结果 模型组小支气管平滑肌及胶原纤维较对照组增厚 ,其厚度均与通气功能指标 0 3秒用力呼气容积 (FEV0 3 )呈显著负相关 ;模型组与TGF β1单抗组比较 ,小支气管及小动脉胶原增生明显 ,与肝素组比较 ,小支气管平滑肌厚度增加。大鼠模型组血清、BALF中PCⅢ、Ln及HA均较对照组有不同程度增高 ;TGF β1、EGF及b FGF在支气管粘膜上皮等组织表达显著增强。各药物干预?
Objective To study the pathological features of the smooth muscles and collagen in small airways of the COPD rat models and their roles in the airway obstruction, to evaluate the relationship between TGF β 1,EGF and bFGF and the airway wall remodeling. Method Rat COPD model (model group) was established by intratracheal instillation of lipopolysaccharide (LPS 200 μg/200 μL) twice and exposure to cigarette smoke daily Drug intervention groups received either daily inhalation of budesonide, ipratropine or heparin respectively, starting on the 8 th day or TGF β 1 monoclonal antibody(TB21)0 5 mg twice (6 th and 19 th day) via the tail veinous injection. At the end of four weeks, the thickness of the smooth muscles and collagen in bronchi and pulmonary arteriole wall were measured by means of image analyzer (CMIAS). Expression and localization of the 3 growth factors were observed in trachea, bronchi and lung tissues by immunohistochemistry and in situ hybridization. The levels of PCⅢ, Ln and HA in the serum and BALF were determined by the RIA method Results Significant thickening of the smooth muscles and collagen were found in the bronchi and pulmonary arterioles of the model group in comparison with those of the control group. There was significant decrease in the thickness of the collagen and smooth muscles in the small airways in TB21 group and heparin group. Statistically negative relationships were shown between the thickness of either smooth muscles or collagen in the small airways and FEV 0 3 (all P <0.05). The levels of PCⅢ, Ln and HA in COPD rat models were higher than those of control groups to varying extent Expressions of TGF β 1,EGF and bFGF in the epithelial cells of bronchi,endothelial cells of pulmonary arterioles and in the macrophages of the model group were significantly higher than those of control group The above mentioned parameters were reduced in different extent in drug intervention groups, in particular, the smooth muscles thickness in heparin g
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2001年第5期283-287,I001,共6页
Chinese Journal of Tuberculosis and Respiratory Diseases
关键词
慢性阻塞性肺疾病
气道重塑
生长因子
Pulmonary disease, obstruetive
Airway wall remodeling
Growth factors
