慢性阻塞性肺疾病大鼠肺组织中IGF-1、IGFBP3表达及其与气道重塑的关系

Expression of IGF-1 and IGFBP3 in lung tissues of rats with chronic obstructive pulmonary disease and its relationship with airway remodeling

目的观察慢性阻塞性肺疾病(COPD)大鼠肺组织中胰岛素样生长因子1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP3)的表达情况,探讨COPD气道重塑的机制。方法将20只雄性Wistar大鼠随机分成模型组和对照组各10只。模型组采用香烟烟熏法制备COPD模型,将大鼠放入熏烟箱内,每次放入10支香烟点燃,持续30min,3次/d,共90 d;对照组常规饲养。处死大鼠,取肺组织,采用HE染色法观察组织形态学变化,并测量细支气管管壁厚度;采用免疫组化法和Real-time PCR法分别检测肺组织中IGF-1、IGFBP3蛋白及mRNA表达;采用Pearson法分析IGF-1、IGFBP3蛋白表达与细支气管管壁厚度的相关性。结果与对照组相比,模型组细支气管管壁厚度增高,肺组织IGF-1、IGFBP3蛋白及mRNA表达增强(P均<0. 01)。IGF-1、IGFBP3蛋白表达与细支气管管壁厚度均呈正相关(r分别为0. 658、0. 654,P均<0. 01),IGF-1蛋白与IGFBP3蛋白表达呈正相关(r=0. 810,P <0. 01)。结论 COPD大鼠肺组织中IGF-1、IGFBP3表达升高,其可能通过促进气道周围细胞的增殖而参与COPD的气道重塑。

Objective To observe the expression of insulin-like growth factor 1(IGF-1)and insulin-like growth factor binding protein 3(IGFBP3)in the lung tissues of rats with chronic obstructive pulmonary disease(COPD),and to explore the mechanism of airway remodeling.Methods Twenty male Wistar rats were randomly divided into model group and control group,with 10 in each.We adopted the method of cigarette smoking to establish the COPD rat models.The rats were put into the smoking box with 10 cigarettes in,each time we lit them for 30 minutes,3 times/d,for 90 days.The control group was fed normally.The rats were killed and lung tissues were taken,the histomorphological changes were observed by HE staining and the wall thickness of small airway was measured.The expression of IGF-1 and IGFBP3 protein in each group were detected by immunohistochemistry.The expression of IGF-1 and IGFBP3 mRNA was detected by real-time fluorescence quantitative PCR;Pearson method was used to analyze the correlation between IGF-1 and IGFBP3 protein expression and bronchiole wall thickness.Results Compared with the control group,the bronchiole wall thickness in the model group increased,and the protein and mRNA expression levels of IGF-1 and IGFBP3 in the lung tissues were enhanced(all P<0.01).IGF-1 protein and IGFBP3 protein were both positively correlated with the thickness of bronchiole wall(r=0.658 and 0.654,respectively;all P<0.01).IGF-1 protein was positively correlated with IGFBP3 protein(r=0.810,P<0.01).Conclusion The expression of IGF-1 and IGFBP3 in the lung tissues of COPD rats increases,which may be involved in the airway remodeling of COPD by promoting the proliferation of cells around the airway.