目的：近年来研究发现细胞外基质（ECM）的过度沉积与肺纤维化发生密切相关，而ECM合成与降解在新生儿慢性肺疾病的肺纤维化发生、发展中作用如何尚不清楚。本文着重研究基质金属蛋白酶-8（MMP-8, Ⅰ型胶原的降解酶）及其组织抑制因子-1（TIMP-1）基因在高氧致新生鼠肺损伤中的表达，并探讨其在纤维化中的作用。方法：80只足月新生大鼠依吸氧浓度（FiO2）随机分为高氧组（FiO2＝0.90）和对照组（FiO2＝0.21）,每组均为40只。采用高浓度氧诱导新生鼠肺损伤模型，应用酶联免疫吸附法（ELISA）、免疫组织化学及反转录聚合酶链反应（RT-PCR）技术，动态研究MMP-8及TIMP-1 mRNA表达，并同时观察肺组织Ⅰ型胶原蛋白的表达强度及其含量变化。结果：实验后14 d 和21 d的高氧组肺组织中，Ⅰ型胶原蛋白表达和Ⅰ型胶原水平均高于对照组， 差异有显著性意义。 而实验后14 d 和21 d，高氧组肺组织MMP-8 mRNA表达降低，TIMP-1 mRNA表达增高，与对照组比较差异有显著性意义。结论：高氧通过下调MMP-8及上调TIMP-1基因表达，导致ECM降解减少，过量ECM沉积于肺组织, 这可能是高氧致肺纤维化的机制之一。［中国当代儿科杂志，2007，9（1）：1-5］

OBJECTIVE: Extracellular matrix (ECM) deposition is a major reason of pulmonary fibrosis in hyperoxia-induced lung injury. However, the relevant mechanism has not been identified. This study examined the gene expressions of matrix metalloproteinases-8 (MMP-8, a catabolic enzyme of type I collagen) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in neonatal rats with hyperoxi-induced pulmonary injury in order to explore the role of MMP-8 and TIMP-1 in pulmonary fibrosis. METHODS: Eighty term newborn rats were randomly exposed to hyperxia (FiO2=0.90, hyperxia group) and to room air (FiO2=0.21, control group) (n =40 each). Lung injury was induced by hyperxia exposure. The content of type I collagen and the expressions of type I collagen protein and MMP-1 mRNA and TIMP-1 mRNA were assayed with enzyme linked immunoadsorbent (ELISA), immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) respectively on days 1, 3, 7, 14 and 21 after exposure. RESULTS: The content of type I collagen and the expression of type I collagen protein in the hyperxia group were statistically higher than those in the control group at 14 and 21 days post-exposure. The MMP-8 mRNA expression decreased while the TIMP-1 mRNA expression increased significantly in the hyperxia group as compared to the control group at 14 and 21 days post-exposure. CONCLUSIONS: Hyperxia exposure down-regulates MMP-8 mRNA expression and up-regulates TIMP-1 mRNA expression. This results in a reduction of ECM degradation, thereby ECM deposition occurs in lung tissue, which may be an important mechanism of pulmonary fibrosis following hyperoxia-induced lung injury.［Chin J Contemp Pediatr, 2007, 9 (1):1- 5］