The Protective Effect Of Prostaglandin E1 On Hyperoxia Induced Brain Injury In Neonatal Rats

Objective:To investigate the protective effect and mechanism of prostaglandin E1(PGE-1)on hyperoxia induced brain injury in neonatal rats.Methods:120 healthy newborn Wistar rats were randomly divided into three groups with 40 rats in each group:The rats in air control group(Con)were kept in room air.The rats in hyperoxia group(Hyp)and hyperoxia+PGE-1(Hyp+PGE-1)were exposed in the hyperoxia(FiO2=85%±5%)hyperoxia model case(home-made)for preparation model of hyperoxia brain injury.From the first day of modeling,the rats in the hyperoxia+PGE-1 group were intraperitoneally injected with PGE-1 at a does of 2 μg/(kg·d)daily,while the other two groups were treated with same volumes saline instead.5 rats were randomly selected to be killed from each group and brain tissues were taken out on the 1st,3rd,7th and 14th day of the experiment.The water content of brain tissue was measured;the pathological changes of brain tissue were evaluated by HE staining;the apoptosis of brain cells was assessed by TUNEL staining;the protein expression of GRP78,CHOP,Caspase-12,JNK and pJNK in brain tissue was measured by Western blot.Result:1.The weights of the Hyp group were lower than that of the Con group at the 1st,3rd,7th and 14th days(P<0.05),the weights of the Hyp+PGE-1 group were higher than that of the Hyp group at the same time point(P<0.05).2.The water contents of the brain tissues of the Hyp group were higher than that of the Con group at the 1st,3rd,7th and 14th days(P<0.05).The water contents of the brain tissues of the Hyp+PGE-1 group were lower than that of the Hyp group at the same time point(P<0.05).3.Pathological observation:1)The results of HE staining:The brain tissues structure of air Con group was normal,brain cells arranged in neat,morphological integrity;the brain tissues inflammatory cell infiltration and cerebrovascular edema were showed in the Hyp group;the brain tissues inflammation and edema in the Hyp+PGE-1 group were milder than those in the Hyp group.2)The results of TUNEL staining:The apoptosis index of the Hyp group at the 1st,3rd,7th and 14th days were significantly increased than that of the Con group(P<0.05),the apoptosis index of the Hyp+PGE-1 group were significantly decreased than that of the Hyp group at the same time point(P<0.05).4.The relative protein expressions of GRP78、CHOP、Caspase-12、JNK and p-JNK protein in the Hyp group were significantly increased than that in the Con group at the 1st,3rd,7th and 14th days(P<0.05).The relative protein expressions of above proteins in the Hyp+PGE-1 group were significantly decreased than that in the Hyp group at the same time point(P<0.05).Conclusion:1.PGE-1 can attenuate brain edema and inflammation induced by hyperoxia and inhibit apoptosis of brain tissue induced by hyperoxia.2.PGE-1 can protect brain cells from apoptosis induced by hyperoxia,and its mechanism may be related to the down-regulation of the expression of GRP78,CHOP,Caspase-12 and JNK protein associated with ERS pathway.