Effect Of Intro-Amniotic Endotoxin And Hyperoxic Exposure On Expression Of Transforming Growth Factor-β1 And A-Smooth Muscle Actin In Lungs Of Newborn Mice

Objective To investigate the expression of transforming growth factor-β1 (TGF-β1) andα-smooth muscle actin (α-SMA) in the lungs of mice with intra-amniotic endotoxin priming and exposed to 60% hyperoxia in order to elucidate the possible relationship with BPD.Methods Timed pregnant C57 mouse were randomly divided into two groups: lipopolysaccharide(LPS) and saline group. LPS(40μl/L) and saline were intra-amniotically injected into the sacs on gestational age day15. The neonatal mouse of each group were randomized to put in 60% oxygen exposure or in room air. (GroupⅠ: LPS+air; GroupⅡ: LPS+hyperoxia; GroupⅢ: saline+air; GroupⅤ: saline+hyperoxia). On days 1, 3, 7, 10 and 14 after birth (8 rats at each time point), the lung histological changes were assessed with hematoxylin and eosin (HE) staining. The expression of TGF-β1 andα-SMA protein were assessed by immunohistochemistry and immunofluorescence and the expressions of TGF-β1 andα-SMA mRNA by Real Time polymerase chain reaction (RT-PCR).Results (1)In groupⅡandⅣRAC began to decrease on day 3, which decresed with increasing hyperoxia expsure time, and those of groupⅡwere the lowest from day 1 to day 14. (2) The expression of TGF-β1 protein and mRNA after day3 of exprosure increased significantly in groupⅡandⅣcompared with groupⅠandⅢ, which increased with increasing hyperoxia exposure time. The expression ofα-SMA protein and mRNA after day7 of exprosure increased significantly in groupⅡandⅣcompared with groupⅠandⅢ, which also increased with increasing hyperoxia exposure time.Conclusion These results suggest that the intra-amniotic endotoxin can enhance the effect that hyperxia exposure can up-regulate TGF-β1andα-SMA , which may results in the pathologenesis of BPD.