MMP-13与TIMP-1表达变化及其在COPD大鼠肺结构改建中的作用

Study on the effct of MMP-13 and its tissue inhibitors,metalloproteinase-1 on the rat of COPD model

目的 :观察胶原酶MMP - 13及其抑制因子TIMP - 1在COPD大鼠模型肺的表达情况 ,探讨它们在COPD发病中的作用。方法 :将 10周龄Wistar大鼠随机分为对照组、模型组 ,通过气道内注入LPS接合烟薰 32天的方法建立COPD大鼠模型 ,测定肺功能后 ,取肺组织石蜡切片HE染色观察肺组织病理改变 ,半定量RT -PCR检测肺组织MMP - 13和TIMP -1mRNA的表达情况。结果 :1、同对照组比较 ,模型组大鼠肺表现类似于人的COPD病理学改变和肺功能改变。 2、半定量RT-PCR检测肺组织中MMP - 13、TIMP - 1mRNA ,发现模型组均较对照组升高 (P <0 .0 1或P <0 .0 0 1)。结论 :COPD大鼠支气管和肺组织表达MMP - 13和TIMP - 1mRNA增多 ,二者间表达不平衡 ,参与了COPD肺结构改变的过程。

Objective:To investigate the expression of the collagenases MMP-13 and its inhibitor, tissue inhibitor metalloproteinase-1 (TIMP-1) in the rat lung of the experimental models of COPD.Methods:Male Wistar rats (10 weeks of age) were divided into two groups—model and control groups.The rat of model group were given intratracheal lipopolysaccharide (LPS),and then animals were exposed to cigarette smoke for 32 days.The lung function was measured,and pathological changes were also observed.Transcriptional levels of MMP-13 and TIMP-1 mRNA extracted from the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).Results:(1)In COPD model group,the pathological changes of bronchi and lung tissue,the changes of lung function were similar to those of the COPD patients.(2)The mRNA expression of MMP-13 and TIMP-1 in COPD model group were significantly increased compared with those in control group( P <0.01 or P <0.001).Conclusion:COPD is characterized by chronic obstruction of expiratory flow affection peripheral airways,associated with chronic bronchitis and emphysema,together with fibrosis and tissue damage,and inflammation of the small airways.MMP-13 and TIMP-1 might play important roles in chronic airway inflammation and remodeling of COPD.They may contribute to the process of pathogenesis,and development of COPD.