Role Of Transforming Growth Factor-beta On HyperoxicLung Fibrosis In Neonatal Rats

Objectives: Hyperoxia is very useful in neonatal medicine, however, long-time hyperoxia inhalation maybe cause lung injury, which can result in respiratory failure, and develop into lung fibrosis and BPD. There attached much attention of people in medical science.At present, the pathogenesis of hyperoxic lung injury in neonate isn't understood completely. TGF- β1correlated with lung auxano and fibrosis. We proposed to establish the rats modle of hyperoxia-induced lung injury.and observe the dynamic changes of the pathologic alteration, wet/dry weight ratio ,TAOCand MDA level, and the expression level of TGF-β1 in the lung of neonatal rats exposed to the hyperoxia inhalation to try to explore:(l) role of TGF- P on hyperoxic lung fibrosis.(2) antioxidant and anti-TGF- P can relieve hyperoxic lung fibrosis?Methods:200 clean Sprague-Dawley(SD) rats which were less than 12 hours old were enrolled in this study.The rats were divided into 5 groups randomly: I normal air control group. II,90%O2.III,90%O2+GSH.V,90%O2+IFN- γ . V >90%O2+GSH+IFN- γ . Group I were placed in the room air .Group II ,111 ,IV and V were placed into oxygen cabins and were exposed to >90% O2 3 days. After at 72 hours,7days,14days and 28days of exposure to high concentration oxygen(O2>95%), wet/dry weight ratio,TAOC and MDA level,and the changes of the pathologic alteration in lung were measured, the expression level of TGF- P iwere measured by immunohistochemistry.Results: The expression level of TGF- β 1, wet/dry weight ratio and MDA level increased at hyperoxia 72 hours and 7 day,but TOAC level was low at hyperoxia 72 hours. Microvessel hyperemia, edema,inflammatory cell infiltration, hemorrhage were found by using light microscope. W/TK MDA and TOAC recovered to the control at hyperoxia 14 day, and that edema,inflammatory cell infiltration,hemorrhage reduced,maked fibrosis changes in lung. At hyperoxia 28 there were a obvious inflammation and wider alveolus alternation and strong express of TGF- P in group II. There were no wet/dry weight ratio and MDA level increased and no significant fibrosis increased with GSH. INF-γ could inhibit the2increase of the expression level of TGF- P i at hyperoxia 72hours.Campared with the control,the expression level of TGF-β i was no increase at hyperoxia 14 day,it be a low level.Lung development was no disorder, no ECM and lung fibrosis was found bye using light microscope and transmission electron microscope.ConclusionrHyperoxia can increase nitric oxide and caused ALL Hyperoxia can increase the expression level of TGF- β \,caused lung development disorder and lung fibrosis, which indicates TGF- β i was key role in fibrosis.GSH inhibited the ALI and lung fibrosis. INF-y can against lung fibrosis and exceptional alveolus develop, which indicates TGF-P imay have aprotective role in hyperoxia-induced lung fiborsis.