β-连环蛋白表达在慢性阻塞性肺疾病大鼠气道重建中的调控作用研究

Regulatory effect of β-catenin gene expression on airway remodeling in rats with chronic obstructive pulmonary disease

目的:探讨β-连环蛋白(β-catenin)基因表达对慢性阻塞性肺疾病(COPD)大鼠气道重建的调控作用。方法:将40只大鼠随机分为COPD组和对照组,每组20只。COPD组采用气管内注入脂多糖(LPS)及熏香烟刺激法建立COPD大鼠模型,对照组不作任何干预。28d后处死大鼠,分离并培养小气道成纤维细胞(FB)。采用酶联免疫吸附试验(ELISA)法检测小气道FB上清液中转移生长因子-β_1(TGF-β_1)、血小板源性生长因子(PDGF)、基质金属蛋白酶(MMP-9)水平,Western blotting法检测小气道FB中β-catenin蛋白相对表达量。Pearson相关分析法分析COPD组小气道FB中β-catenin蛋白相对表达量与上清液中TGF-β_1、PDGF、MMP-9水平的关系。结果:COPD组小气道FB上清液中TGF-β_1、PDGF、MMP-9水平及小气道FB中β-catenin蛋白相对表达量均明显高于对照组(均P<0.05)。β-catenin蛋白相对表达量与TGF-β_1、PDGF、MMP-9水平呈正相关关系(r=0.243、0.249、0.358,均P<0.05)。结论:COPD大鼠气道重建中FB增殖关键因子水平较高,且与β-catenin蛋白表达呈正相关关系,推测β-catenin在气道重建中有调控作用。

Objective: To investigate the regulation of β-catenin gene expression in airway remodeling in rats with chronic obstructive pulmonary disease (COPD). Methods: 40 rats were randomly divided into COPD group and control group,with 20 rats in each group.COPD rat model was established by intratracheal injection of lipopolysaccharide (LPS) and cigarette exposure.The levels of transfer growth factor-β 1 (TGF-β 1),platelet-derived growth factor (PDGF) and matrix metalloproteinase (MMP-9) in the small airway fibroblasts (FB) supernatant were detected by enzyme-linked immunosorbent assay.The expression of β-catenin protein in the small airway FB were determined by western blotting.Pearson correlation analysis was performed to analyze the association between the expression of β-catenin and the levels of TGF-β 1 ,PDGF and MMP-9 in the small airway BF. Results: The levels of TGF-β1 ,PDGF and MMP-9 as well as the expression of β-catenin protein in the COPD group were significantly higher than those in the control group (P<0.05).The protein expression of β-catenin was positively correlated with TGF-β1 ,PDGF and MMP-9 levels (r=0.243,0.249 and 0.358, P<0.05). Conclusion: The levels of FB proliferation factors were high,and were positively correlated with β-catenin protein expression.We speculated that β-catenin exerted a regulatory action in airway remodeling.