[The changes and effects of metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 protein and mRNA expression in the lung tissue of neonatal rats with chronic lung disease induced by hyperoxia].

OBJECTIVE: To investigate the dynamic changes and the effects of metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2) mRNA in lungs of neonatal rats after inhaling high concentration of oxygen. METHODS: Full-term newborn rats were continuously exposed to oxygen (0.90-0.95) or room air (0.21O(2)) within 12 hours after birth. Lung histological study with hematoxylin-eosin staining (HE) and radical alveolar counts (RAC) were performed; the changes in MMP-2 and TIMP-2 protein and mRNA expression were measured by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) on 1, 3, 7, 14 and 21 days in hyperoxia groups and air inhalation controls. RESULTS: Compared with air inhalation controls, inflammation response was seen in early stage, the arrest of lung development was evident after 7 days of oxygen exposure, finally resulting in interstitial fibrosis; RAC began to decrease from 7 days in hyperoxia rats compared to air inhalation controls (P<0.05), more so on 14 days and 21 days (both P<0.01); MMP-2 protein and mRNA expression were higher on 3 days (P<0.05 and P<0.01), and protein decreased on 14 days (P<0.05), while mRNA didn't change; the expression of TIMP-2 protein and mRNA showed no change all the time. CONCLUSION: With prolonged hyperoxia, the balance of MMP-2/ TIMP-2 can not be maintained. Collagen breakdown is disturbed, which may lead to lung inflammatory injury in early stage and then collagen deposition in lung interstitium and lung development is arrested resulting in chronic lung disease.