摘要
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 Extracellular matrix （ECM） deposition is a major reason of pulmonary fibrosis in hyperoxiainduced lung injury. However, the relevant mechanism has not been identified. This study examined the gene expressions of matrix metaUoproteinases-8 （MMP-8, a catabolic enzyme of type Ⅰ collagen） and tissue inhibitor of metalloproteinases-Ⅰ （TIMP-Ⅰ） in neonatal rats with hyperoxia-induced pulmonary injury in order to explore the role of MMP-8 and TIMP-Ⅰ 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 significandy 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.
出处
《中国当代儿科杂志》
CAS
CSCD
2007年第1期1-5,共5页
Chinese Journal of Contemporary Pediatrics
基金
National Natural Science Foundation of China (No. 30440056).
