肺纤维化大鼠中基质金属蛋白酶-2的表达

目的：研究基质金属蛋白酶－2（MMP2）在肺纤维化中的作用。方法：（1）用免疫组织化学方法（ABC法）观察博莱霉素所诱导的实验性大鼠纤维化肺组织内MMP2表达的动态变化;（2）用逆转录－聚合酶链反应（RT－PCR）观察博莱霉素所诱导的肺纤维化不同时期间质成纤维细胞MMP2 mRNA的动态变化。（3）用Northern印迹杂交和免疫细胞化学方法观察转化生长因子β1（TGFβ1）对体外培养的大鼠肺成纤维细胞MMP2mRNA和蛋白表达的影响。结果：（1）诱导纤维化组1－7d,病灶内浸润的单核巨噬细胞及肺泡间质细胞数量增多,MMP2免疫组织化学染色阳性,14d以后,阳性单核巨噬细胞减少,用博莱霉素28d时,阳性间质细胞亦减少。（2）博莱霉素作用后1d,肺成纤维细胞MMP2基因转录即明显增强,为对照组的2．05倍,28d时下降。（3）TGFβ1作用后,大鼠肺成纤维细胞MMP2mRNA及其蛋白表达增强。结论：肺组织内MMP2的过度表达,可能是肺纤维化启动的重要原因。

Expression of matrix metalloproteinase-2 in rat pulmonary fibrosis

OBJECTIVE: To study the role of matrix metalloproteinase-2 (MMP(2)) in rat pulmonary fibrosis. METHODS: (1) Dynamic changes of MMP(2) expression were observed in bleomycin-induced rat pulmonary fibrosis by use of immunohistochemical technique. (2) RT-PCR was carried out to show the dynamic changes of MMP(2) mRNA expression of isolated pulmonary fibroblasts (PFbs) during rat pulmonary fibrosis. (3) Northern blot analysis and immunocyto chemistry techniques were performed to detect the expression of MMP(2) mRNA and their relevant protein in cultured rat PFbs after treatment with transforming growth factor 1 (TGF beta(1)). RESULTS: (1) On day 1-7th after receiving bleomycin, the infiltrated pulmonary macrophages and septa mesenchymal cells showed positive reaction with anti-MMP(2) and an increase in number. After 14 days and on 28 th of bleomycin treatment, the number of positive staining macrophages and mesenchymal cells were decreased respectively. (2) The gene expression of MMP(2) mRNA of PFbs were enhanced after bleomycin treatment from the Day 1 and decreased by Day 28. (3) The expression of MMP(2) mRNA and their relevant protein were enhanced in rat PFbs after TGF beta(1) treatment. CONCLUSIONS: Over expression of MMP(2) in pulmonary tissue may be an important factor in the initiation of pulmonary fibrogenesis.