Effect of miR-582-5p targeting regulation of FOXO1 on neuronal damage in neonatal rats with hypoxic ischemic encephalopathy
Objective To investigate the effect of microRNA-582-5p(miR-582-5p)on neuronal damage in neonatal rats with hypoxic ischemic encephalopathy(HIE)through targeted regulation of forkhead box transcription factor O1(FOXO1).Methods Newborn rats(n=90)were randomly grouped into the control(NC)group,the model(HIE)group,the miRNA non-specific control(LV-miRNA-NC)group,the miR-582-5p overexpression(LV-miR-582-5p)group,the miR-582-5p overexpression+mRNA control(LV-miR-582-5p+LV-NC)group and the miR-582-5p overexpression+FOXO1 overexpression(LV-miR-582-5p+LV-FOXO1)group.HIE model was established in all groups except the NC group,and neurological deficits were scored on rats.TTC staining was applied to measure the volume of cerebral infarction.Real-time PCR was applied to detect miR-582-5p and FOXO1 expression.Dual fluorescence reporter gene experiment was applied to detect the targeting relationship between miR-582-5p and FOXO1.HE staining method was applied to observe pathological changes in hippocampal tissue.TUNEL and NeuN fluorescence dual labeling co localization were applied to detect neuronal apoptosis in hippocampal tissue.Immunohistochemistry was applied to detect expressions of FOXO1 and Caspase-3 proteins.Results There was a targeting relationship between MiR-582-5p and FOXO1.Compared with the NC group,the neurological deficit score,cerebral infarction volume,FOXO1 expression,neuronal apoptosis rate,FOXO1 and Caspase-3 protein expression were increased in the HIE group,and the miR-582-5p expression obviously decreased,the hippocampal tissue showed obvious pathological damage(P＜0.05).Compared with the LV-miRNA-NC group,the neurological deficit score,cerebral infarction volume,FOXO1 expression,neuronal apoptosis rate,FOXO1 and Caspase-3 protein expression obviously decreased in the LV-miR-582-5p group,and the miR-582-5p expression obviously increased,the pathological damage of hippocampus tissue was obviously improved(P＜0.05).LV-FOXO1 was able to reverse the protective effect of LV-miR-582-5p on neuronal damage in HIE rats.Conclusion MiR-582-5p can directly target FOXO1,negatively regulate FOXO1 expression,reduce neuronal apoptosis in HIE neonatal rats,and have a protective effect on neural injury.
hypoxia-ischemia,braintrauma,nervous systemforkhead box protein O1microRNA-582-5p
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维普
