| Part ⅠTHE EXPRESSION AND SIGNIFICANCE OF TRANSFORMINGGROWTH FACTOR BATA1 AND INTERFERON GAMMA IN HYPEROXIALUNG INJURYOBJECTIVE: Massive researchs showed that IFN-γ and TGF-β1 played an important role in fibrotic diseases, but the mechanism of t IFN-γ and TGF-β1 in hyperoxia lung injury was not clear. we observed the dynamic change of IFN-γ and TGF-β1 in animal model of hyperoxia lung injury to understand the mechanism of the fibrosis .METHODS: 32 juvenile Wistar rats were randomly divided into room-air groups and hyperoxia groups, the latter were further divided into 3 subgroups of hyperoxia-exposure for 3, 7 and 14 days. The mRNA levels of IFN-γ and TGF-β1 in the lungs were measured by reverse-transcription polymerase chain reaction (RT-PCR). Meanwhile the comparative analysis was conducted respectively to the protein content in the bronchoalveolar lavage fluid(BALF), the lung permeability coefficient, the ratio of lung wet /dry weight(W/D) and the pulmonary histopathologic changes.RESUITS: Compared with the control(4.92±0.38), there was no remarkable elevated of the lung's W/D of 3-day-hyperxia-exposure group (5.09±0.19, P＞0.05), while those of of 7-day-hyperxia-exposure group(5.60±0.25, P＜0.05) elevated and 14-day-hyperxia-exposure group(5.46±0.30)decreased significantly, but without statistical difference Compared with the control(4.92±0.38), The protein content in BALF of the groups under hyperoxia-exposure for 3(0.45±0.10), 7(0.66±0.08) and 14(0.79±0.14)days were much higher than that of the control(0.18±0.08, P＜0.05). The permeability coefficient of the groups under hyperxia-exposure for 3 (6.61±2.05), 7(10.88±1.54) and 14(12.75±2.20)days were much higher than that of the control(2.99±1.27, P＜0.05). Compared with the control, the lungs of 3-day-hyperxia-exposure group developed into edema, hemorrhage and inflammatory infiltration and this condition aggravated at the 7th day. The pulmonary septum was significantly widened at the 14th day, the interstitial fibrocytes as well as alveolar epithelial cells proliferated obviously, and the tendency of lung fibrosis was also presented. The results mentioned above showed that the modle of hyperoxia lung injury was successfully established, and the acute inflamationm was its early symptom while the fibrosis was its late manifistation. There was no positive cytes of IFN-γ in the lung of nomal rats, The positive cytes of the groups under hyperxia-exposure for 3, 7, 14 day, which climbed to the climax at the 7th day and began to decline from the 14th day, were found in alveolus epithlia,pulmonary interstitial, bronchoepithlia and macrophage. The level of IFN-γ mRNA of the groups under hyperxia-exposure for 3(0.62±0.49), 7(0.44±0.53) and 14(0.39±0.27)days were higher than that of the control(0.20±0.14). The expression of IFN-γ mRNA notably elevated and up to its peak (P＜0.05)at the 3th day, then gradually declined from the 7th day and much more obviously after the 14th. TGF-β1 took on extensive positive in alveolus epithlia in the control group. The positive cytes of the groups under hyperxia-exposure for 3, 7, 14 day distributed in alveolar epithelium, pulmonary interstitial, bronchoepithlia and macrophage, which were notably enhanced along with the time of hyperxia-exposure. The level of TGF-β1 mRNA of the groups under hyperxia-exposure for 3(0.78±0.24), 7(0.97±0.27) and 14(1.16±0.11)days were higher than that of the control(0.58±0.17, P＜0.05). Compared with the control, the ratio of IFN-γ and TGF-β1 elevated significantly at the 3th day, began to decrease from the 7th and striking declined at the 14th.CONDCLUSIONS: At the early period of hyperoxia-induced lung injury, the increased IFN-γ promoted the progress of lung inflammation; while at the late stage, the disequilibrium between IFN-γ and TGF-β1 might attribute to acceleration of the development of lung fibrosis .
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