Abstract: Objective: To explore the protective effect of glutamine(GLN) on the hyperoxia-induced lung injuryof the neonatal rats through endoplasmic reticulum stress (ERS) pathway, and to elucidate its mechanisms. Methods: A total of 90 Wistar rats were randomly divided into control group (FiO₂=21%), hyperoxia group(FiO₂>85%), and hyperoxia+GLN group (FiO₂>85%,the concentration of intraperitoneal injection of GLN was 0.75 g·kg^-1·d^-1);there were 30 rats in each group. The body weights and water contents in the lung tissue of the neonatal rats were measured on the 3rd, 7th and 14th days of the experiment. HE staining was used to determine the morphology of lung tissue of the rats. The superoxide dismutase (SOD) activity in lung tissue of the rats was detected by nitro blue tetrazolium chloride(NBT), and the malondialdehyde (MDA) level was determined by thiobarbital acid(TBA). The expression levels of Caspase-12, GADD153, GRP78, Bcl-2,and Bax in lung tissue of the rats were detected by Western blotting method. Results: Compared with control group at the same time, the body weights of the neonatal rats in hyperoxia group on the 3rd,7th and 14th days were significantly decreased(P<0.05), the water contents in lung tissue of the neonatal rats were increased(P<0.05), the SOD activities were significantly decreased(P<0.05), the levels of MDA in the lung tissue of the neonatal rats were increased(P<0.05), the expressions levels of Caspase-12, GADD153, GRP78 and Bax proteins were significantly increased(P<0.05),and the expression levels of Bcl-2 protein and the Bcl-2/Bax ratios were significantly decreased(P<0.05).Compared with hyperoxia group at the same time, the body weights of the neonatal rats in hyperoxia + GLN group on the 3rd,7th and 14th days were significantly increased(P<0.05), the water contents in lung tissue of the neonatal rats were decreased(P<0.05), the SOD activities were significantly increased(P<0.05), the levels of MDA in lung tissue of the neonatal rats were decreased(P<0.05), the expression levels of Caspase-12, GADD153, GRP78 and Bax proteins were significantly decreased(P<0.05), the expression levels of Bcl-2 protein and the Bcl-2/Bax ratios were increased(P<0.05).The pathological sections of lung tissue of the rats in control group showed that lung tissue structure was regular, no alveolar edema was found,the alveolar size and alveolar septum were approximately the same, and no inflammatory cell infiltration was found; the histopathological sections of lung tissue of the rats in hyperoxia group showed swelling of brochial and alveolar epithelial cells, enlargement of alveolar lumen, edema of interstitial cells, inflammatory cell infiltration and fibrous exudation;the degrees of alveolar damage, the inflammatory exudation and the proliferation of fibrons tissue in hyperoxia+GLN group were alleviated which was between hyperoxia group and control group. Conclusion: GLN can alleviate the hyperoxia-induced lung tissue edema and inflammatory response of the neonatal rats, and one of mechanisms is that GLN can down-regulate the expression levels of Caspase-12, GADD153, GRP78 and Bax proteins and up-regulate the expression level of Bcl-2 protein through ERS pathway to protect hypoxic lung injury.

Key words: hyperoxic lung injury, neonatal rats, glutamine, endoplasmic reticulum stress, Caspase-12, growth arrest-and DNA damage-inducible gene153, glucose regulation protein 78, B-cell lymphoma-2, Bcl-2 associated X protein