Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest
Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest
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DOI：
10.1111/aor.13910
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发表时间：
2021-03-08
影响因子：
2.4
通讯作者：
Liu, Xiao-Cheng
中科院分区：
文献类型：
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作者：
Li, Yi-Ai;Liu, Zhi-Gang;Liu, Xiao-Cheng
神经功能障碍常见于心脏手术后伴深低温循环骤停（DHCA）。dhca相关脑损伤的机制尚不清楚。本研究确定了DHCA大鼠海马中环状rna （circRNAs）表达谱的变化，试图探索circRNAs在DHCA相关脑损伤中的潜在作用。采用DHCA体外循环对成年雄性大鼠进行体外循环。通过神经系统严重程度评分和组织学及透射电镜检查评估脑损伤。通过芯片技术筛选海马组织中circRNAs的表达谱。采用实时荧光定量PCR （RT-qPCR）验证芯片结果的可靠性。应用生物信息学算法构建竞争性内源性RNA （ceRNA）网络，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析以探索环状RNA的潜在生物学作用。在筛选的14145个环状rna中，56个在DHCA和假手术大鼠的海马中差异表达，包括30个上调环状rna和26个下调环状rna。选择的6个circrna（上调：rno_circRNA_011190、rno_circRNA_012988、rno_circRNA_000544；下调：rno_circRNA_010393、rno_circRNA_012043、rno_circRNA_015149）的表达变化进一步通过RT-qPCR证实。生物信息学分析显示，这些已证实的环状rna及其潜在靶mrna在几种KEGG通路中富集，包括组氨酸代谢、脂肪细胞因子信号和cAMP信号。通过揭示DHCA后大脑中circRNAs表达谱的变化，本研究表明这些失调的circRNAs可能参与脑损伤，并提示靶向circRNAs预防和治疗与DHCA相关的神经功能障碍的潜力。
Neurological dysfunction commonly occurs after cardiac surgery with deep hypothermic circulatory arrest (DHCA). The mechanisms underlying DHCA-associated brain injury remain poorly understood. This study determined the changes in expression profiles of circular RNAs (circRNAs) in the hippocampus in rats that underwent DHCA, with an attempt to explore the potential role of circRNAs in the brain injury associated with DHCA. Adult male Sprague Dawley rats were subjected to cardiopulmonary bypass with DHCA. Brain injury was evaluated by neurological severity scores and histological as well as transmission electron microscope examinations. The expression profiles of circRNAs in the hippocampal tissues were screened by microarray. Quantitative real-time PCR (RT-qPCR) was used to validate the reliability of the microarray results. Bioinformatic algorithms were applied to construct a competing endogenous RNA (ceRNA) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the potential biological roles of the circRNAs. Out of 14 145 circRNAs screened, 56 were differentially expressed in the hippocampus between the DHCA and sham-operated rats, including 30 upregulated and 26 downregulated circRNAs. The expression changes of six selected circRNAs (upregulated: rno_circRNA_011190, rno_circRNA_012988, rno_circRNA_000544; downregulated: rno_circRNA_010393, rno_circRNA_012043, rno_circRNA_015149) were further confirmed by RT-qPCR. Bioinformatics analysis showed the enrichment of these confirmed circRNAs and their potential target mRNAs in several KEGG pathways including histidine metabolism, adipocytokine signaling, and cAMP signaling. By revealing the change expression profiles of circRNAs in the brain after DHCA, this study indicates possible involvements of these dysregulated circRNAs in brain injury and suggests a potential of targeting circRNAs for prevention and treatment of neurological dysfunction associated with DHCA.