高氧致CLD新生大鼠肺组织中MMP-8和TIMP-2表达的动态改变及其对纤维化形成作用的研究

目的探讨MMP-8（基质金属蛋白酶-8）和TIMP-2（基质金属蛋白酶抑制物-2）的表达在高氧致CLD新生大鼠肺组织中的动态变化及其对CLD最终纤维化形成的作用。方法足月新生鼠生后12h内分别持续吸入90%-95％的高氧和空气，于1、3．7、14、21d，取肺组织Masson染色和Gomori银染色，图像定量分析，计算胶原及网状纤雏阳性面积百分比，以评估纤维沉积；应用免疫组化和RT—PCR技术检测肺组织中MMP-8和TIMP-2蛋白和mRNA表达的动态变化。结果7d开始高氧组的胶原和网状纤维在肺间隔和间质沉积，14和21d阳性面积高于空气组。高氧组MMP-8蛋白和mRNA表达在7d后低于空气组，两组TIMP-2的表达在各时间点上无差异。结论新生大鼠随着吸入高氧时间的延长，肺组织MMP-8表达降低，而TIMP-2表达不变。MMP-8／TIMP-2的平衡状态遭到破坏，胶原降解减少，从而促进了胶原在肺间质的沉积。

Effects of MMP-8 and TIMP-2 expression on fibrosis in lung tissue of neonatal rats with CLD induced by hyperoxia

[Objective] To investigate the dynamic changes and the effects of matrix metalloproteinase-8(MMP 8)and tissue inhibitors of metalloproteinase-2 (TIMP-2)on interstitial fibrosis in lung of neonatal rats with CLD in duced by hyperoxia. [Methods] Full-term newborn rats were continuously exposed to oxygen (90%～95%) or room air (21% O2) after birth within 12 hours. Using Masson and Gomori staining, the areas of collagenic fibres and reticular fibres were measured by imaging analysis; the changes of MMP-8 and TIMP-2 protein and mRNA expression were measured by immunohistochemistry and RT-PCR on day 1, 3, 7, 14 and 21 in two groups. [Results] After 7 d of oxygen exposure, collagenic fibres and reticular fibres began to deposit in interstitum, the areas were larger than those in air groups on 14 d and 21 d; The expression of MMP-8 protein and mRNA are decreased from 7 d to 21 d in hyperoxia groups; The expression of TIMP-2 protein and mRNA showed no change all the time. [Conclusion] With prolonged hyperoxia, the balance of MMP-8/TIMP-2 can not be kept, collagen breakdown is inhibited, which maybe leads to collagen deposition in lung interstitium.