| Background: It has been reported that repeated administration of clinical administration of ketamine can induce neuronal apoptosis in immature brains.Human pregnancy 3 months to 3 years after birth is the rapid development of the nervous system.Animal studies have shown that the use of anesthetics during this period can cause structural changes in the central nervous system and long-term cognitive dysfunction.The aim of this study was to investigate the effect of ketamine on the expression of HIF-1? in hippocampus of neonatal rats and its effect on cognitive function in rats.Methods: P7 rats were treated with ketamine and YC-1 for 6 hours to observe the expression of HIF-1? in hippocampus and the cognitive function of rats when it reached 7 weeks old.The mechanism of mi R-199a-5p was explored by luciferase reporter assay.In vitro,the expression level of HIF-1? was observed in hippocampal neurons treated with ketamine and YC-1.The effect of mi R-199a-5p on the regulation of HIF-1? expression induced by ketamine was studied by overexpression and inhibition of mi R-199a-5p.Cell proliferation assay and Annexin V/PI double staining apoptotic cell assay were used to identify the effect of HIF-1? on neuronal apoptosis.Results: Repeated administration of therapeutic doses of ketamine in neonatal rats for 6 hours resulted in upregulation of HIF-1? in hippocampal and long-term cognitive dysfunction in rats,and the ketamine inhibitor YC-1 could rescue these effects.Ketamine or the inhibitor of mi R-199a-5p can down-regulate the expression of mi R-199a-5p,thereby increasing the expression of HIF-1?.While mi R-199a-5p mimics or YC-1 can rescuing the changes caused by ketamine.Conclusion: Ketamine down-regulates mi R-199a-5p,thereby increasing the expression of downstream HIF-1? and promoting neuronal apoptosis.Therefore,ketamine-induced neonatal neuronal apoptosis and long-term cognitive dysfunction are caused by mi R-199a-5p/HIF-1? axis. |
PDF Full Text Request