肺间质纤维化大鼠肺组织基质金属蛋白酶的动态改变

Effects of metalloproteinases on pulmonary fibrosis by bleomycin in rats

目的进一步评价基质金属蛋白酶（ＭＭＰ）在肺间质纤维化形成过程中的作用。方法Ｗｉｓｔａｒ大鼠２１只随机分为模型组１４只，对照组７只，模型组在额镜直视下插管，注入０４％博莱霉素注射液５ｍｇ／ｋｇ，制成动物模型。观察注射药物后１周和４周肺泡巨噬细胞和成纤维细胞ＭＭＰ的活性及表达。利用空斑扩散法，测定胶原酶活性。结果正常肺巨噬细胞和成纤维细胞分泌的胶原酶活性很低，分别为２０４×１０－７Ｕ／细胞和３０６×１０－７Ｕ／细胞，动物模型１周、４周组，肺巨噬细胞和成纤维细胞分泌的胶原酶活性明显增加。肺巨噬细胞１周达高峰（２５８０×１０－７Ｕ／细胞），成纤维细胞４周达高峰（２８９０×１０－７Ｕ／细胞）；正常肺组织ＭＭＰ１ｍＲＮＡ、ＭＭＰ２ｍＲＮＡ表达很低，动物模型１周，４周组，ＭＭＰ１ｍＲＮＡ、ＭＭＰ２ｍＲＮＡ表达较对照组增加，４周组较１周组略有降低。结论ＭＭＰ在肺间质纤维化形成早期肺泡炎阶段及后期纤维化形成阶段均起重要调节作用。

Objective Matrix metalloproteinases (MMPs) are the mediators for dynamic equilibrium of extracellular matrix. The purpose was to investigate the effects of metalloproteinases on the development of pulmonary fibrosis. Methods The expression and activity of metalloproteinases of alveolar macrophage, and fibroblasts were evaluated on rats with pulmonary fibrosis induced by bleomycin. Results The activity of collagenase was low in the macrophage and fibroblast in control group, 20.4×10 -7 U/cell and 30.6×10 -7 U/cell respectively. There was an increase in the first and fourth week groups of bleomycin rats. The highest level of activity of alveolar macrophages was 258.0×10 -7 U/cell in first week group. A peak of enzymatic activity was found in 4th week group (289.0×10 -7 U/cell). The mRNA of MMP 1, MMP 2 were expressed at lower levels in the normal lung tissue and there was an increase in first week, and fourth week group of bleomycin rats with a peak in one week group. Conclusions The regulation of metalloproteinases might play an important role in the development of pathological processes in pulmonary fibrosis.