碱性成纤维细胞生长因子在慢性支气管炎、肺气肿大鼠模型血管重塑中的作用

Role of bFGF on artery remodeling in rat model of chronic obstructive pulmonary disease

目的通过构建慢性支气管炎、肺气肿大鼠模型，探讨碱性成纤维细胞生长因子（basic fibroblast growth factor，bFGF）在慢性支气管炎、肺气肿血管重塑中的可能作用。方法将8周龄、雄性、体质量（220±15）g Wistar大鼠40只随机分为慢性支气管炎、肺气肿组（A组）、bFGF干预组（B组）、anti-bFGF干预组（C组）和对照组（D组），每组10只。A组：经血管内注入脂多糖和反复烟熏复制成慢性支气管炎、肺气肿模型；B组：每周一次经尾静脉内注入0．1μg bFGF，其他制备方法同慢性支气管炎、肺气肿组；C组：每周一次经尾静脉内注入0．1μg anti-bFGF，其他制备方法同慢性支气管炎、肺气肿组；D组：舱外饲养4周。4周后处死动物，取肺组织切片后苏木精-伊红染色及免疫组织化学染色，在光学显微镜下对各组小血管及肺泡组织进行病理学评分和比较；检测并比较各组肺小动脉平滑肌指数及胶原指数；测定并比较各组支气管平滑肌bFGF的相对含量。结果A组肺组织病理评分、肺小动脉平滑肌指数、胶原指数和bFGF吸光值分别为362±31、0．5125±0．0256、25．79±0．8854和38．14±1．012。B组分别为453±24、0．6536±0．0356、35．13±0．7687和63．33±2．048，与A组比较均显著增高，差异有统计学意义（P〈0．05）。c组分别为306±28、0．4171±0．0133、18．53±0．6321和26．38±1．102，与A组比较均显著降低，差异有统计学意义（P〈0．05）。结论bFGF参与了大鼠慢性支气管炎、肺气肿模型血管重塑过程，而anti-bFGF可以抑制这一过程。

Objective To observe the expression and distribution of basic fibroblast growth factor （bFGF） in rat lung with chronic obstructive pulmonary disease（COPD） for its potential role in airway remodeling in COPD. Methods Forty male, 8 weeks old Wistar rats were divided randomly into the following groups：COPD group（group A） ;bFGF interfere in COPD group（group B） ;anti-bFGF interfere in COPD group （group C）, and negative control group （group D）. COPD models were established by intratracheal instillation of lipoplysacchairde（LPS） and exposured to cigarette smoking daily,B and C models by respectively instillation particular quantity bFGF and anti-bFGF into different COPD model group from caudal vein once a week. After these models became true, the pathologic alterations of arterioles by hematoxylin and eosin stain Van-Gieson ＋ elastic fibers stain were observed. At the same time,the thickness of the smooth muscle and collagen in 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 in situ hybridization Detection. Results In group A, the integral of pulmonary pathology the index for the smooth muscle of pulmonary small artery, the collagen thickness exponent of small artery and the positive decoration absorbed value of bFGF were 362 ± 31,0. 5125 ±0. 0256,25.79 ±0. 8854 and 38.14± 1. 012, in group B, they were 453 ± 24, 0. 6536 ± 0. 0356, 35.13 ± 0. 7687 and 63.33±2.048, compared with group A,all the indexes in group B showed significant increase （all P 〈0.05）. In group C, they were 306 ± 28,0. 4171 ± 0. 0133,18.53 ± 0. 6321 and 26.38 ± 1. 102, compared with group A, all the indexes in group C showed significant decrease （all P 〈0. 05）. Conclusions bFGF might participate in the process of small artery remodeling in COPD;anti-bFGF might restrain the process of small artery remodeling in COPD animal model, this would have a positive effect for preventing and deteriorating the small artery remodeling.