The Effect Of Glutamine On ERS Pathway With Hyperoxic Lung Injury In Neonatal Rats

Objective:To explore the effect of glutamine on ERS pathway with hyperoxic lung injury in neonatal rats.Methods:Randomly selected a total of 90 male and female Wistar rats and divided into air group(A,n=30,FiO2=21%),hyperoxia group(B,n=30,FiO2>85%),hyperoxia+glutamine(GLN)group(C,n=30,FiO2>85%).The rats in group C were processed through intraperitoneal injection of 0.75g/kg/d glutamine solution fromthe first day of experiment,and the rats in group A and B were intraperitoneallyinjected with the same dose of saline.Body mass and W/D values in the lung tissues of neonatal rats were measured at 3th、7th and 14th;the pathological changes of lung tissues were measured by HE staining;The expressions of IL-1β,IL-6 and TNF-a in the lung tissues were detected by enzyme linked immunosorbent assay(ELI SA),the content of SOD was detected by hydroxylamine method and the content of MDA was determined by TBA method.The expressions of Caspase-12,GAD D153,GRP78,Bcl-2/Bax protein were detected by western blot.Result:1.Compared with group A,The body mass of neonatal rats at 3th、7th and 14th in group B were significantly lower(P<0.05).The body mass of neonatal rats in the group C was higher than that in group B(P<0.05).2.The W/D ratios of the lung tissues in the group B were higher than that in the group A at the 3th,7th and 14th(P<0.05).The difference was gradually increased with the prolongation of time.The W/D ratios in group C were significantly lower than that in group B(P<0.05).3.Compared with group A,the pathological changes of lung tissues were more obvious with the prolongation of hyperoxia exposure in group B,such as alveolar fusion,fibrous tissue hyperplasia and interstitial inflammatory exudation.The pathological changes of lung tissues in group C were more alleviate than group B.4.Compared with group A,the levels of IL-1β,IL-6 and TNF-α in lung tissues homogenate of group B were significantly higher(P<0.05).Compared with group B,the levels of IL-1β,IL-6 and TNF-α in group C were significantly decreased(P<0.05).5.The activities of SOD in group B were decreased with the prolongation of hyperoxia exposure,which were lower than that in group A(P<0.05),the difference was most significant at 14th(P<0.05),the activities of SOD in group C was higher than that in group B(P<0.05).The MDA activities in group B were higher with the prolongation of hyperoxia exposure.Compared with group A,the activities of MDA in group B were significantly higher than that in group A(P<0.05).The activity of MDA in group C increased gradually,which were lower than that in group B(P<0.05).6.The expressions of Caspase-12,GADD153 and GRP78 in group B were significantly higher than that in group A(P<0.05),and the expression of Bcl-2 was significantly decreased(P<0.05).While the expression of Bax protein increased slightly,but there was significant difference(P<0.05).The expressions of Caspase-12,GADD153,GRP78 and Bax proteins in group C were significantly lower than that in group B(P<0.05),while the expression of Bcl-2 protein was significantly increased(P<0.05).Conclusion:1.GLN can alleviate the hyperoxia-induced neonatal rats lung tissues edema and inflammatory response.2.GLN may down-regulate the expressions of Caspase-12,GADD 153,GRP78,Bax proteins and up-regulate the expression of Bcl-2,through ERS pathway to protect hyperoxia lung injury.