Effects and possible mechanisms of sevoflurane-induced miR-211-5p on developmental neurotoxicity in neonatal mice
Objective To investigate the effect of sevoflurane-induced miR-211-5p on developmental neurotoxicity in neonatal mice and its possible mechanism.Methods Neonatal mice on the 6th day after birth were randomly divided into control group,sevoflurane group,sevoflurane+antagomiR-NC group and sevoflurane+antagomiR-211-5p group,with 6 mice in each group.RT-qPCR was used to detect the expression level of miR-211-5p in hippocampus of neonatal mice;HE staining was used to detect the pathological damage of hippocampus of neonatal mice;TUNEL assay was used to detect the apoptosis of nerve cells in hippocampus of neonatal mice;RT-qPCR was used to detect the mRNA expression of IL-6 and TNF-α in hippocampus of neonatal mice;bioinformatics was used to predict the potential binding sites of miR-211-5p and NQO1 mRNA,and double luciferase reporter gene assay was used to verify the prediction;Western blot was used to detect the expressions of NQO1 and PI3K/AKT/mTOR signaling pathway related proteins in hippocampus of neonatal mice.Results Sevoflurane upregulated the expression of miR-211-5p in hippocampus of neonatal mice,promoted the pathological damage,nerve cell apoptosis and inflammatory factor expression levels in hippocampus of neonatal mice;antagomiR-211-5p decreased the expression of miR-211-5p in hippocampus of neonatal mice induced by sevoflurane,inhibited the pathological damage,nerve cell apoptosis and inflammatory factor expression levels in hippocampus of neonatal mice.miR-211-5p targeted NQO1 mRNA.Sevoflurane decreased the expression of NQO1 protein in hippocampus of neonatal mice,inhibited the activation of PI3K/AKT/mTOR signaling pathway;antagomiR-211-5p increased the expression of NQO1 protein in hippocampus of neonatal mice treated with sevoflurane,activated PI3K/AKT/mTOR.Conclusion Sevoflurane induces developmental neurotoxicity by down-regulating NQO1 by miR-211-5p and inhibiting PI3K/AKT/mTOR signaling pathway.
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