碱性成纤维细胞生长因子在COPD大鼠模型气道重塑中的作用

目的通过构建慢性阻塞性肺疾病(COPD)大鼠模型,探讨碱性成纤维细胞生长因子(bFGF)在COPD气道重塑的作用和可能机制。方法2005年7月至8月,于广西医科大学动物实验中心,将40只8周龄、雄性、平均体重为(220±15)g的Wistar大鼠随机分为COPD组(A组)、COPD bFGF组(B组)、COPD anti-bF-GF组(C组)和对照组(D组),每组10只。A、B、C3组COPD模型制备:经气管内注入脂多糖(LPS)和反复烟,复制成。A组为COPD对照组;B组:每周1次经尾静脉内注入0·1μgbFGF;C组:每周1次经尾静脉内注入0·1μganti-bFGF;D组:舱外饲养4周。4周后对各组大鼠气道进行病理学评分;检测并比较各组支气管平滑肌指数(平滑肌厚度/气道内径)及胶原指数(胶原厚度/气道内径);用免疫组化法观察bFGF在支气管肺内表达。结果与D组相比,A组、B组、C组大鼠的小气道都存在不同程度病理改变,差异均有显著性意义。与A组比较,B组肺组织病理评分显著增高、平均肺泡面积显著扩大、支气管平滑肌指数和胶原指数显著增高、bFGF吸光值均显著增高,而C组肺组织病理评分显著降低、平均肺泡面积显著缩小、支气管平滑肌指数和胶原指数显著降低、bF-GF吸光值均显著减少。结论bFGF参与了大鼠COPD模型气道炎症和气道重塑过程,而anti-bFGF可以抑制这一过程。

Potential role of bFGF in airway remodeling of chronic obstructive pulmonary disease rat model

Objective To observe the expression and distribution of the basic fibroblast growth factor(bFGF)in lung through chronic obstructive pulmonary disease(COPD)rat models and to investigate the potential role of bFGF in the mechanism for airway remodeling in COPD.Methods Forty male,8 weeks old Wistar rats were divided into groups randomly:COPD group;bFGF interfere in COPD group;anti-bFGF interfere in COPD group,and control group.COPD models were established by intratracheal instillation of lipopolysacchairde(LPS)twice in a month and exposure to cigarette smoking daily and in order to contrast respectively instillate particular quantity bFGF and anti-bFGF into different COPD model group from caudal vein in every week.After these models became true,observe the pathologic alteration of small airways,arterioles and pulmonary alveolus by hematoxylin and eosin stain Van-Gieson elastic fibers stain.At the same time,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 bFGF as well as the effects of antibody on them were observed by Histostaining and ISH(in situ hybridization)detection.Results There was a significant increase in the thickness of the smooth muscle and collagen in bronchi of bFGF interfere in COPD group compared with that of control group and COPD group(P<0.05);there was great decrease in anti-bFGF interfere in COPD group compared with that of control group and COPD group.The expression of the bFGF was greatly increased in tunica mucosa bronchiorum epithelium,pulmonary arteriole and lung alveolus macrophage(P<0.01).The relative content for bFGF interfere in COPD group was significantly higher than that of COPD group(P<0.01).The alternation of anti-bFGF interfere in COPD group was greatly lower than that of COPD group.Conclusion bFGF might participate in the process of airway remodeling in COPD;anti-bFGF might restrain the process of airway remodeling in COPD animal model;this would have a positive effect on preventing and deteriorating the airway remodeling.