基质金属蛋白酶及金属蛋白酶组织抑制剂在肺纤维化中的变化

Changes of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Pulmonary Fibrosis

观察基质金属蛋白酶 (MMPs)及金属蛋白酶组织抑制剂 (TIMPs,MMPs特异性抑制剂 )在鼠肺纤维化中的变化 ,以探讨 MMPs与肺纤维化之间的关系。采用气管内灌注博莱霉素的方法复制鼠肺纤维化模型 ,并进行了以下研究 :1HE染色、 Masson染色 ,2羟脯氨酸含量测定 ,3MMP- 2 ,TIMPs免疫组织化学分析 ,4 MMPs蛋白电泳 ,5肺组织溶胶原活性测定。结果显示 :实验组大鼠在肺泡炎阶段 MMP- 2的蛋白表达增强、活性增加 ,TIMPs的蛋白表达相对减弱 ,肺组织溶胶原活性升高 ;在肺纤维化阶段 ,MMP- 2较炎症时减弱 ,而 TIMPs增强 ,肺组织溶胶原活性下降。提示

The changes of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in rat pulmonary fibrosis, and the relationships between MMPs and pulmonary fibrosis were studied. Rats were divided into fibrosis group and control group. Rat pulmonary fibrosis model was developed by an intratracheal injection of bleomycin. Following tests were performed: HE and Masson staining of lung sections; determination of lung tissue hydroxyproline (HYP); immunohistochemical staining of lung MMP 2 and TIMPs; protein electrophoresis of MMPs; collagenolytic activity assay of pulmonary homogenates. The results revealed that in the alveolitis phase, the expression and activity of MMP 2 and the collagenolytic activity in the fibrosis group were higher than in contral group, while the expression of TIMPs was correspondingly decreased. In the fibrosis phase, the expression and activity of MMP 2 and the collagenolytic activity were lower than those in control group, but the expression of TIMPs was increased. The results suggested that the imbalance of MMPs/TIMPs contributes to the development of pulmonary fibrosis.