肺间质纤维化大鼠肺组织基质金属蛋白酶及其组织抑制因子含量变化

观察肺纤维化形成过程中基质金属蛋白酶（Matrix Metallo proteinas简称MMPs)及其组织抑制因子（Tissue inhibitors of Metallo proteinases简称TIMPs)含量的变化，探讨其在肺纤维化发病中的作用。将Wistar大鼠60只，随机均分为对照组及模型组，气管内注入博莱霉素A5 5mg/kg,制备肺间质纤维化动物模型，观察注药后1、3、7、14及28d肺脏病理变化，利用酶谱法及免疫印记法分析肺组织MMP－2、MMP－9、TIMP－1的含量变化。结果显示各模型组pro-MMP-2、MMP－2、TIMP－1蛋白含量均较对照组增加，尤其7、14及28d组MMP－2较前明显增多。而MMP－9变化不很明显。提示在肺纤维化形成过程中，pro-MMP-2、MMP－2及TIMP－1都有所增高，MMP／TIMP比例失衡是最终导致肺间质纤维化形成的重要因素。

Changes of lung tissue matrix metallo proteinase and its tissue inhibitor in pulmonary fibrosis rats

To explore the role of matrix metallo proteinase (MMPs) and their tissue inhibitor(TIMPs) in pathogenesis of pulmonary fibrosis. The animal model of pulmonary fibrosis was established by injecting bleomycin A5 into rat trachea(5mg/kg), furthermore, pulmonary pathologic changes and MMP 2?MMP 9 ?TIMP 1 were assessed for various time 1?3?7?14 and 28 days. MMPs and TIMPs were assessed by zymogram and Western Blot analysis. The Results showed that protein expression of ProMMP 2?MMP 2 and TIMP 1 were significantly increased in pulmonary fibrosis groups compared that in normal groups, especially level of MMP 2 ,which was augmented at 7?14 and 28 days. Nevertheless, the difference of MMP 9 between two groups had not been observed. We concluded that the markedly higher level of MMP 2 and TIMP 1 might be involved in the pathogenesis of disease. Moreover, it was suggested that the unbalance between MMP/TIMP seemste be the most important factor resulting in pulmonary fibrosis.