Differential expressions of miRNAs in peripheral blood of neonatal rats in the hypoxia-ischemia injury with self-resuscitation model / 中华实用儿科临床杂志

ABSTRACT

Objective:To assess the changes in profiles of microRNAs (miRNAs) in peripheral blood of neonatal Sprague-Dawley (SD) rats with hypoxia-ischemia(HI) injury with self-resuscitation.Methods:Neonatal rats of 3 pregnant rats were divided into 3 groups according to their nests, in which group A was the blank control group, group B was the HI group, and group C was the alternative group.The expression profiles of miRNAs in periphe-ral blood of neonatal rats in group A and B by high-throughput sequencing was compared.Bioinformatics analysis was applied to investigate these differentially expressed miRNAs.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to screen out enriched signaling pathways and functions.Target genes of miRNAs and those correlated with hypoxia-ischemia brain damage were predicted using miRBaseData (miRBD) software.HE staining was performed to observe the pathological changes of rat brain tissues.Results:A total of 1 049 mature reliable miRNAs in peripheral blood of neonatal rats were identified, including 525 miRNAs in group A, and 524 in group B. There were 27 differentially expressed miRNAs between group A and B, and their types were highly correlated.A total of 38 dysregulated miRNAs were screened out in group B, involving 21 upregulated miRNAs and 17 downregulated ones.GO and KEGG analyses showed that the identified differentially expressed miRNAs were mainly enriched in the glutamatergic synapse pathway, myelin lipid metabolism, neural activity ligand-receptor interaction and the vascular epithelial growth factor (VEGF) signaling pathway, all of them were significantly correlated with HIBD and over-activated.Cortex and subcallosal white matter lesions, enlarged ventricles, disordered arrangement of gray matter neurons, and obvious apoptosis in rat brain tissues of group A and B were not observed in HE staining.Conclusions:Differential expression of miRNAs in peripheral blood of HI self-resuscitated rats suggests that miRNAs has a positive response to hypoxia and ischemia.Differentially expressed miRNAs, including miR-200, miR-471, miR-429, miR-216 and miR-871 families, in peripheral blood of neonatal rat with HI showed their active response after HIBD.They are related to the molecular mechanisms of the nervous system damage, and are expected to become novel diagnostic markers for HIBD or HI.Differentially expressed miRNAs are conductive to the development of therapeutic targets of HI.