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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14d和21d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14d和21d,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。
OBJECTIVE: In recent years, it has been found that the excessive deposition of extracellular matrix (ECM) is closely related to the occurrence of pulmonary fibrosis. However, it is unclear how the synthesis and degradation of ECM play an important role in the occurrence and development of pulmonary fibrosis in neonatal chronic lung disease. This article focuses on the expression of matrix metalloproteinase-8 (MMP-8, type Ⅰ collagen degrading enzyme) and its tissue inhibitor of metalloproteinase-1 (TIMP-1) gene in hyperoxia-induced neonatal rat lung injury, The role of change. Methods Eighty full term newborn rats were randomly divided into high oxygen group (FiO2 = 0.90) and control group (FiO2 = 0.21) by oxygen concentration (FiO2), 40 in each group. High concentration oxygen was used to induce neonatal rat lung injury model. The expression of MMP-8 and TIMP-1 mRNA was studied dynamically by enzyme linked immunosorbent assay (ELISA), immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) , And at the same time observe the expression of collagen type Ⅰ in lung tissue and its content. Results The level of collagen Ⅰ and type Ⅰ collagen in the lung tissue of hypoxia group 14 and 21 days after the experiment were higher than those in the control group, and the difference was significant. On the 14th day and the 21st day after the experiment, the expression of MMP-8 mRNA and the expression of TIMP-1 mRNA in the lung tissue of the hyperoxia group were significantly lower than those in the control group. Conclusions Hyperoxia decreases the degradation of ECM and the excessive deposition of ECM in lung tissue through the down-regulation of MMP-8 and up-regulation of TIMP-1 gene expression, which may be one of the mechanisms of hyperoxia-induced pulmonary fibrosis.