氨茶碱对慢性阻塞性肺疾病大鼠气道重塑的影响

Effect of aminophylline on airway remodeling in chronic obstructive pulmonary rats

目的 探讨氨茶碱对慢性阻塞性肺疾病(COPD)大鼠症状的改善及对气道重塑的影响,并分析转换生长因子β1(TGF-β1)/Smads通路的作用。方法 将55只大鼠建立COPD模型,随机分成模型组、激动剂组、激动剂+氨茶碱组和氨茶碱组,每组各10只,剩余10只作正常组。给予相应干预后,检测大鼠的肺功能;ELISA检测大鼠血清白细胞介素-8(IL-8)、白细胞介素-1β(IL-1β)和气道平滑肌中基质金属蛋白酶组织抑制剂1(TIMP-1)、基质金属蛋白酶9(MMP-9)水平;HE染色观察大鼠肺部病理,测量支气管平滑肌厚度;Western blot检测大鼠TGF-β1/Smads通路相关蛋白表达。结果 激动剂组、模型组、激动剂+氨茶碱组、氨茶碱组、正常组大鼠V、PEF水平逐渐升高,血清IL-8、IL-1β及支气管平滑肌TIMP-1、MMP-9水平逐渐降低(P<0.05)。抑制剂组、模型组气道黏膜上皮脱落,皱襞增多,管壁大量炎性细胞浸润,肺泡结构紊乱,气道壁增厚;激动剂+氨茶碱组、氨茶碱组上述情况有所改善。激动剂组、模型组、激动剂+氨茶碱组、氨茶碱组、正常组大鼠支气管平滑肌厚度逐渐增加,p-NF-κB、TGF-β1、p-Smad2蛋白表达逐渐下调(P<0.05)。结论 氨茶碱可改善COPD大鼠肺功能,拮抗气道重塑,可能是通过抑制TGF-β1/Smads通路实现的。

Objective To investigate the effect of aminophylline on the improvement of symptoms and airway remodeling in rats with chronic obstructive pulmonary disease(COPD), and to analyze the role of transforming growth factor-β1(TGF-β1)/Smads pathway.Methods Fifty five rats were randomly divided into model group, agonist group, agonist+aminophylline group and aminophylline group, with 10 rats in each group, and the remaining 10 rats were served as healthy group. After the corresponding intervention, the lung function of rats was detected. The levels of serum interleukin-8(IL-8), interleukin-1β(IL-1β) and tissue inhibitor of matrix metalloproteinase-1(TIMP-1) and matrix metalloproteinase-9(MMP-9) in airway smooth muscle were detected by ELISA. HE staining was used to observe the lung pathology and measure the thickness of bronchial smooth muscle. Western blot was used to detect the expression of TGF-β1/Smads pathway related proteins.Results In the agonist group, model group, agonist + aminophylline group, aminophylline group and healthy group, the levels of Vand PEF were gradually increased, while the levels of serum IL-8, IL-1β and TIMP-1, MMP-9 of bronchial smooth muscle were gradually decreased(P<0.05). In the inhibitor group and model group, the airway mucosa epithelium fell off, the folds increased, a large number of inflammatory cells infiltrated into the airway wall, the alveolar structure was disordered, and the airway wall thickened. In the agonist+aminophylline group and aminophylline group, the above situation was improved. In agonist group, model group, agonist + aminophylline group, aminophylline group and healthy group, the thickness of bronchial smooth muscle gradually increased, and the protein expressions of p-NF-κB, TGF-β1 and p-Smad2 were gradually decreased(P<0.05).Conclusion Aminophylline can improve lung function and antagonize airway remodeling in COPD rats, which may be achieved by inhibiting TGF-β1/Smads pathway.