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目的 探讨基质金属蛋白酶 2 ,9(MMP - 2 ,MMP - 9)在高氧所致急性肺损伤发病过程中的作用。方法将 5 4只小鼠置于密闭的氧气室暴露于 >95 %的高氧 ,另取18只小鼠置于呼吸室内 (空气 )作为对照组。分别于 2 4 ,4 8和 72h取出小鼠评价肺损伤程度 ,以基质金属蛋白酶谱分析调查支气管肺泡灌洗液中MMP - 2及MMP - 9的释放及活性。逆转录 -聚合酶链反应 (RT -PCR)及免疫组织化学法测定肺组织MMP - 2及MMP - 9的表达及组织分布。结果 高氧能引起急性肺损伤伴支气管肺泡灌洗液MMP -2及MMP - 9释放及活性增加 ,RT -PCR结果显示高氧组动物肺组织MMP - 2及MMP - 9的mRNA表达增高 ,免疫组织化学研究显示MMP - 2和MMP - 9蛋白主要表达于气道上皮细胞、血管平滑肌细胞和炎性细胞的胞浆中 ,它们在气道上皮细胞的表达在高氧环境下明显升高。结论 基质金属蛋白酶 2 ,9在高氧所致的急性肺损伤过程中发挥重要作用
Objective To investigate the role of matrix metalloproteinase 2, 9 (MMP - 2, MMP - 9) in the pathogenesis of acute lung injury induced by hyperoxia. Methods 54 mice were placed in a closed oxygen chamber exposed to> 95% hyperoxia, and another 18 mice were placed in the respiratory chamber (air) as a control group. Mice were sacrificed at 24, 48, and 72 hours, respectively, to assess the extent of lung injury. Matrix metalloproteinases (MMP) were used to investigate the release and activity of MMP - 2 and MMP - 9 in bronchoalveolar lavage fluid. The expression and distribution of MMP - 2 and MMP - 9 in lung tissue were determined by RT - PCR and immunohistochemistry. Results Hyperoxia induced the release and activity of MMP - 2 and MMP - 9 in acute lung injury and bronchoalveolar lavage fluid. RT - PCR results showed that the mRNA expression of MMP - 2 and MMP - 9 increased significantly in hyperoxia group Histochemical studies showed that MMP - 2 and MMP - 9 were mainly expressed in the cytoplasm of airway epithelial cells, vascular smooth muscle cells and inflammatory cells. The expression of MMP - 2 and MMP - 9 in airway epithelial cells was significantly increased under hyperoxia. Conclusion Matrix metalloproteinases 2 and 9 play an important role in the process of hyperoxia-induced acute lung injury