Objective To explore the effects of normobaric hyperoxia(NBO)on cerebral microvascular endothelial cells injury and nu-clear factor E2-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathways in neonatal rats.Methods A total of 45 neonatal SD rats were enrolled and divided into normoxia group,NBO group and NBO+Nrf2 activator group by random number table method,15 rats in each group.The rats in normoxia group were fed in ordinary air(21％oxygen),while rats in NBO group and NBO+Nrf2 activator group were fed in 90％normobaric oxygen.The rats in NBO+Nrf2 activator group were given intragastric administration of 5 mg/kg Nrf2 agonist sulforaphane daily.The content of Evans blue(EB)in brain tissues was detected,the levels of vascular endothelial growth factor(VEGF)and matrix metalloprotein-ase-9(MMP-9)were detected by enzyme-linked immunosorbent assay,water content of brain tissues was detected by wet-dry weighting method,the pathological changes of brain tissues were observed by HE staining and TUNEL staining,expressions of Nrf2/HO-1 signaling path-way proteins in hippocampus were detected by Western Blotting,and cognitive function of rats was detected by water maze test.Results Com-pared with normoxia group,levels of EB,VEGF and MMP-9,and water content of brain tissues were increased in NBO group,the differences were statistically significant(P＜0.05).Compared with NBO group,levels of EB,VEGF and MMP-9,and water content of brain tissues were decreased in NBO+Nrf2 activator group,the differences were statistically significant(P＜0.05).The results of pathological staining showed that in normoxia group,morphology and structure of nerve cells were intact,and there were no obvious pathological changes or apoptosis.In NBO group,morphology and structure of nerve cells were irregular,and there was obvious edema and vacuoles,with a large number of apoptosis cells.The pathological injury of brain tissues in NBO+Nrf2 activator group was significantly milder than that in NBO group.Compared with normoxia group,relative expression levels of Nrf2 and HO-1 proteins in brain tissue were decreased in NBO group,the differences were statistically signifi-cant(P＜0.05).Compared with NBO group,relative expression levels of Nrf2 and HO-1 proteins in brain tissue were increased in NBO+Nrf2 activator group,the differences were statistically significant(P＜0.05).Compared with normoxia group,escape latency was prolonged,and fre-quency of crossing the platform was decreased from 2th-4th day in NBO group,the differences were statistically significant(P＜0.05).Com-pared with NBO group,escape latency was shortened,and frequency of crossing the platform was increased from 2th-4th day in NBO+Nrf2 acti-vator group,the differences were statistically significant(P＜0.05).Conclusion NBO can induce cerebral microvascular endothelial cells inju-ry in neonatal rats,which leads to long-term cognitive dysfunction.It may be related to the down-regulation of Nrf2/HO-1 signaling pathways.
维普
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