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目的 探讨基质金属蛋白酶 ( MMPs)及其组织抑制剂 ( TIMPs)在早产大鼠生后肺发育中的作用。方法 早产 SD大鼠出生后 3、 7、 14、 2 1d,各取动物 6只 ,行肺组织形态学观察、辐射状肺泡计数 ( RAC)、免疫组化法检测肺组织 MMP- 2、MMP- 9、TIMP- 1和 TIMP- 2的表达。结果 3 d时肺基本结构单位为终末囊泡 ,至 14d时为肺泡 ,典型小直径肺泡数目显著增加 ,2 1d时肺泡壁变薄。RAC值 7d( 7.1± 0 .9)较 3 d( 5 .0± 0 .8) ,14d ( 9.9± 0 .6)较7d明显增加 ( P均 <0 .0 1) ,2 1d ( 10 .5± 0 .8)与 14d无显著差异。气道上皮细胞、肺泡上皮细胞、成纤维细胞等弱阳性～中等强度表达 MMP- 2、MMP- 9、TIMP- 1和 TIMP- 2。MMP- 2、TIMP- 2的表达在 14d时 ( 1.65± 0 .75 ,0 .75± 0 .63 )明显增强 ( P<0 .0 1,P<0 .0 5 ) ,TIMP- 1的表达 2 1d时 ( 2 .66± 0 .5 5 )显著增强 ( P<0 .0 1)。结论 MMPs、TIMPs参与了大鼠生后肺发育 ,可能介导了肺泡化过程
Objective To investigate the role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in lung development after preterm birth in preterm rats. Methods SD rats were sacrificed at 3, 7, 14 and 21 days after birth and 6 animals in each group were sacrificed. The lung morphology, radial alveolar count (RAC) and immunohistochemistry were used to detect the expression of MMP-2 and MMP- 9, TIMP-1 and TIMP-2 expression. Results At 3 days, the basic lung structure unit was the final vesicle, which was alveolar at 14 days. The number of typical small diameter alveoli was significantly increased, and the alveolar wall became thinner on 21 days. The RAC value at 7d (7.1 ± 0.9) was significantly higher than that at 7d (5.0 ± 0.8) and 14d (9.9 ± 0.6) at 7d (P <0.01) 5 ± 0 .8) and 14d no significant difference. Airway epithelial cells, alveolar epithelial cells, fibroblasts and other weak positive ~ moderate expression of MMP-2, MMP-9, TIMP-1 and TIMP-2. The expression of MMP-2 and TIMP-2 were significantly increased at 14d (1.65 ± 0.75, 0.75 ± 0.63, P <0.01, P <0.05) 2d (2.66 ± 0.55) were significantly enhanced (P <0.01). Conclusions MMPs and TIMPs are involved in lung development after birth in rats and may mediate the alveolar process