Profiles of messenger RNAs and micro RNAs in cerebral cortices of rats with hypoxic ischemic encephalopathy in different periods

Abstract

Objective To identify key micro RNAs (miRNAs) and thier regulatory pathways through analyzing messenger RNAs (mRNAs) and miRNAs expression profiles in animal models of hypoxic ischemic encephalopathy (HIE). Methods Eighteen 7-d old SD rats were divided into hypoxic-ischemic group and sham-operated group (n=9) by random number table. And rats in each group were divided into 0 h sub-group, one d sub-group and 7 d sub-group (n=3) according to different times after model making. Modified Rice method was used to establish the HIE rat models in the hypoxic-ischemic group, and only the left common carotid artery was isolated in the sham-operated group. The cerebral cortices of the two groups were taken for high-throughput sequencing to establish mRNAs and miRNAs expression profiles. TargetScan, miRanda and PITA were used to match differential miRNAs with corresponding homologous mRNAs, and to analyze and predict their related target genes and signal pathways. Results (1) As compared with those in the sham-operated group, the enzymatic analysis of the mRNAs sequencing results of the brain tissues in the hypoxic-ischemic group showed that the biological characteristics of the HIE models in the 0 h sub-group were likely to be reflected in cell localization, cell proliferation, migration, and vascular development, and associated with complement and antigen presentation, tumor necrosis factor (TNF) signaling pathway and cytokine receptors; those in the one d sub-group were likely to be reflected in single organism signal, and response to external stimuli, and vascular development, and associated with complement, antigen presentation, adhesion, and extracellular matrix receptors; those in the 7 d sub-group were likely to be involved in cell localization, single organism signaling, and cell adhesion, and associated with complement, antigen presentation and cytokine receptor. (2) After comparing the differentially expressed miRNAs detected by miRNAs sequencing with the mRNAs sequencing results of the same group, it was found that there were differences in the expressions of rno-mir-181b-5p, rno-mir144-3p, rno-mir-873-5p, rno-mir-411-5p, rno-mir-132-3p, rno-mir-486, rno-mir-127-5p and rno-mir-6321; functional analysis found that these miRNAs mainly involved in inflammatory response and regulation of neurological function in various periods. Conclusion Through the complex negative regulatory network, miRNAs may participate in the key pathogenesis of HIE at various stages through various inflammatory mechanism and play an important role in the neuronal plasticity of the neonatal hypoxic ischemic brain tissue and the development of the nervous system. Key words: Hypoxic ischemic encephalopathy of newborn; Message RNA; Micro RNA; High throughput sequencing