| Objective:To investigate the protctive effects and mechanism of 1,25(OH)2D3 on hyperoxia-induced lung injury in newborn rats.Methods:Sixty newborn Wistar rats were randomly divided into 3 groups(20 per group):The rats in air group(A)were kept in room air,the hyperoxia group(B)and hyperoxia+1,25(OH)2D3 group(C)were exposed to hyperoxia(85%O2)for 14 days.Group C were injected intraperitoneally 5ng/g/day of 1,25(OH)2D3,and group A and B were given the same volumes of saline.The lung tissues were taken out on 3rd,7th and 14th after the experiment.The wet and dry ratio of lung tissue were determined.The histopathological was observed using by HE staining.The levels of IL-6,IL-1β,SOD and MDA were measured by commercial enzymelinked immunosorbent assay(ELISA)kits.The expression of Bax,Bcl-2,GRP78,CHOP and Caspase 12 were assessed by Western blot.Results:1.The weight of group B was significantly lower than that of group A,and the group C was higher than that of group B.2.The ratio of wet and dry of lung tissues was significantly higher in the group B than that of group A and increased with the exposure time of high oxygen,and the group C was lower than that of group B(P<0.05).3.Histopathological observation showed that the lung tissue structure of group A was normal,and the vessels and peribronchial of group B was edema,the lung tissue structure was disordered,the air cavities were enlarged and alveolus were damaged,the inflammatory cells were increased.The pathological changes of lung tissue structure in group C were significantly better than that of group B.4.The levels of IL-6 and IL-1β of lung tissues were significantly higher in group B than that of group A,and increased with exposure time of high oxygen,and the group C were lower than that of group B(P<0.05).The activity of SOD of lung tissues were significantly lower in group B than that of group A,and group C were higer than that of group B(P<0.05).The levels of MDA were higher in group B than that of group A,and group C were lower than that of group B(P<0.05).5.The ratio of Bcl-2/Bax was significantly lower in group B than that of group A,and it was higher in group C than that of group B(P<0.05).The expression of GRP78,CHOP and Caspase12 were significantly higher in group B than that of group A,and it was lower in group C than that of group B(P<0.05).Conclusion:Our results show that 1,25(OH)2D3 can reduce hyperoxia-induced pulmonary edema,inflammation,and the lung tissue apoptosis.The mechanism may be related to down-regulation the expression of GRP78,CHOP and Caspase12 proteins which interacted with endoplasmic reticulum stress. |
