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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,计算胶原及网状纤维阳性面积百分比,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。
Objective To investigate the dynamic changes of the expression of MMP-8 and TIMP-2 in the lung tissue of neonatal rats with hyperoxia-induced CLD and their effects on the final fibrosis of CLD effect. Methods Full-term neonatal rats were inhaled continuously for 90% ~ 95% of the hyperoxia and air within 12 hours after birth. Masson staining and Gomori silver staining of lung tissue were taken on day 1,3,7,14,21. And the percentage of reticular fibers positive area to evaluate the fiber deposition. The dynamic changes of the expression of MMP-8 and TIMP-2 protein and mRNA in lung tissue were detected by immunohistochemistry and RT-PCR. Results At day 7, the collagen and reticular fibers in hyperoxia group were interstitial and interstitial deposition, and the positive area at 14 and 21 days was higher than that in air group. The expression of MMP-8 protein and mRNA in hyperoxia group was lower than that in air group after 7 days. The expression of TIMP-2 in two groups had no difference at all time points. Conclusions The expression of MMP-8 in lung tissue is decreased and the expression of TIMP-2 remains unchanged in neonatal rats with inhalation of hyperoxia. The balance of MMP-8 / TIMP-2 is destroyed and the degradation of collagen is reduced, thus promoting Collagen deposition in the lung interstitial.