The Role Of LncRNA Riken In Sevoflurane-induced Embryonic Neurotoxicity

Background: Retrospective studies found that children with prolonged or repeated surgery and anesthesia showed a higher incidence of cognitive impairment than unexposed ones in their adolescents.The rapid development period of human nervous system is from the third trimester of pregnancy to 2-3 years after birth.Many animal studies have shown that inhaled anesthetics can affect the structure and function of brain in fast development,and may even affect the brain's future function.Long non-coding RNA(LncRNA)has a very important biological function in embryonic neurodevelopment.The aim of this study is to investigate the role of LncRNA Riken in the neurotoxicity of sevoflurane and the effect of the length of sevoflurane exposure on its embryonic neurotoxicity.Methods: Mouse embryonic stem cells were induced to differentiate into neural stem cells.The neural stem cells were treated with 4.1% sevoflurane for 1 or 6 hours.The expression of LncRNA Riken,IGF-1 and Sox1 were observed.At the same time,the function of LncRNA Riken was explored by RNA pulldown experiment and luciferase reporter gene experiment.In addition,we also carried out sevoflurane treatment on pregnant mice(gestation stage day 14)to observe the expression of LncRNA Riken,IGF-1 and brain development related factors in fetal brain.Results: The results showed that 4.1% sevoflurane exposure for 6 hours in mouse neural stem cells were able to reduce the inhibitory effect on mi RNA-29 a by down-regulating the expression of LncRNA Riken,and thus down-regulated the expression of IGF-1 and inhibited neuronal differentiation.The overexpression of LncRNA Riken reversed these phenomenon.The expression of LncRNA Riken and IGF-1 was decreased in the 6-hour group treated with sevoflurane.There was no decrease in LncRNA Riken and IGF-1 expression in cells and pregnant mice for 1-hour sevoflurane exposure.Conclusions: Sevoflurane can inhibit neuronal differentiation and thus affect its subsequent neuronal growth,which may be caused by the impact on LncRNA-Riken/mi RNA-29a/IGF-1 pathway.The results of this study show that LncRNA Riken may be a potential therapeutic target in sevoflurane-induced neurotoxicity,and more research is needed to explore the mechanisms.