The Study Of Pathogenesis Of TGF-β1 And MMPs Involved In Hyperoxia-induced Lung Injury

Part IThe pathogenesis of Transforming growth factor-pi and Matrix metalloproteinase involved in hyperoxia lung injuryObjective: Mechanical ventilation with hyperoxia is the common treatment to the respiration distress syndrome in children and adult, the worst complication of which were lung development disorder and lung fibrosis .These attached much importance of people in medical science. The pathogenesis of hyperoxia lung injury and fibrosis is not clear. Based on the study of the key role of TGF-pl and MMPs in fibrosis disease, we establish the rats model of hyperoxia-induced lung injury, observed the dynamic changes of TGF-pl and MMPs protein and mRNA levels in the lungs, investigated the relationship between the changes and hyproxia-induced lung injury as well as the effect mechanism.Methods: 32 Wistar rats of two weeks were randomly divided into room-air group and hyperoxia group. After 3, 7 ,14 days of continuous exposure to high concentration oxygen (O2>95%), the protein level and the gene expression of TGF-pl and MMPs in lung was measured by immunohistochemistry and reverse transcript polymerse chain reaction (RT-PCR)respectively . The protein content in bronchoalveolar lavage fluid(BALF) , permeability index, lung wet/dry weight ratio and histological changes of hyperoxia-induced lung injury were performed.Results: There are low protein levels of TGF- β 1 and MMP-2, MMP-9 in normal lung tissue. The protein level of TGF-pl in hyperoxia group increased significantly than the control, and raised gradually until 14th day. The protein level of MMP-2 and MMP-9 increased markedly from 3rd day , raised to the peak at 7th day, and decreased at 14th day. The changes of gene expression of TGF- β1 and MMPs consistended with thatof protein levels. The lung pathological changes manifested hyperaemia, edema, infiltration of inflammatory cells during the earlier period of lung injury, and alleviation of inflammation , marked fibrosis changes in lung during the later period. Conclusions: The unbalance between TGF-β1 and MMPs may play an important role of development lung fibrosis during the later period of hyperoxia-induced lung injury.