摘要
目的探讨氧化应激和基质金属蛋白酶-9（MMP-9）／基质金属蛋白酶抑制物-1（TIMP-1）在高氧肺损伤新生大鼠的肺组织中动态变化以及两者的相互关系。方法将足月新生大鼠在出生后，分别持续吸人90％～95％高氧或空气，于1、3、7、14、21d取肺组织进行HE染色，应用分光光度计比色法检测肺组织丙二醛（MDA）含量、免疫组化技术检测MMP-9和TIMP-1动态表达。结果病理观察高氧3d时出现炎症反应，7d时出现肺泡发育阻滞，最终纤维化；高氧3、7、14d后MDA含量高于空气组（P〈0．05，P〈0．01，P〈0．05）；MMP-9表达主要在上皮细胞胞浆，高氧3d时较空气组增强（P〈0．05）；TIMP-1表达主要在上皮细胞、内皮细胞和肺泡巨噬细胞胞浆，3d后各时间点的表达均高于空气组（P〈0．05，P〈0．05，P〈0．01，P〈0．01）；MDA含量与MMP-9、TIMP-1蛋白表达呈正相关（P〈0．05，P〈0．01）。结论高氧暴露后可能通过氧化应激上调MMP-9和TIMP-1表达引起基膜的破坏，从而导致毛细血管通透性的增加和以后呼吸道重塑的发生。
Objective To investigate the changes and relation of oxidaflye stress and MMP-9/TIMP-1 in the lung of neonatal rats with hyperoxic hmg injury. Method Full-term newborn rats were continuously exposed to 90% to 95% oxygen or room air rsepectively after birth within 12 hours. Malondialdehyde （MDA） contents were constantly monitered by spectrophotometer at 1, 3, 7, 14 and 21 days in hyperoxia group and air controls, and MMP-9 and TIMP-1 expressions were measured by immtmohistochemistry. Results Contents of MDA in the hmgs ofhyperoxia group were elevated at 3, 7, 14 days post-exposure （P 〈0.05, P 〈 0.01, P 〈0.05）; the positive expression of MMP-9 was mainly in the epithelial ceils, a significant increase at 3 days （ P 〈 0.05 ） compared with air group. TIMP-1 was mainly expressed in epithelial ceils, interstitial ceils and pulmonary macrophages, and the expressions of TIMP-1 in hyperoxia group were higher than those in air groups from 3 days to21 days （P〈0.05, P〈0.05, P〈0.01, P〈0.01）; MDA contents were positively correlated to MMP-9 and TIMP-1 expression （ P 〈 0.05, P 〈 0.01）. Conclusions MMP-9 and TIMP-1 expression may been upregulated by oxidative stress after hyperoxia exposure in newborn rats, and this may result in disruption of the alveolar basement membrane, which leads to the capillary leakage and airway remodeling.
出处
《中华急诊医学杂志》
CAS
CSCD
2007年第7期690-693,共4页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金资助项目（No.3044056,30672253）
