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心肌缺血再灌注损伤大鼠上胸段脊髓中新型长链非编码RNA的特征分析

Characterization of novel lncRNAs in upper thoracic spinal cords of rats with myocardial ischemia-reperfusion injuries.

作者信息

Li Zhi-Xiao, Li Yu-Juan, Wang Qian, He Zhi-Gang, Feng Mao-Hui, Xiang Hong-Bing

机构信息

Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

出版信息

Exp Ther Med. 2021 Apr;21(4):352. doi: 10.3892/etm.2021.9783. Epub 2021 Feb 11.

Abstract

Myocardial ischemia-reperfusion injury (MIRI) is a significant problem in clinical cardiology, and refers to a more serious myocardial injury caused by blood recanalization after a period of myocardial ischemia, as compared with injury caused by vascular occlusion. The spinal cord, as the primary afferent and efferent center of cardiac sensory and sympathetic nerve fibres, has received increased attention in recent years with regards to the regulation of MIRIs. Previous studies have revealed that MIRI has a strong correlation with the abnormal expression of long non-coding (lnc)RNAs in the myocardium; however, there are limited reports on the effects of the altered expression of lncRNAs in the spinal cord following MIRI. To investigate the expression patterns of lncRNAs in the spinal cord after MIRI and their potential role in the early stage of reperfusion, a MIRI model was established in rats. After 30 min of myocardial ischemia and 2 h of reperfusion, the upper thoracic spinal cord tissues were immediately dissected and isolated. lncRNAs and mRNAs in spinal cord tissues were screened using transcriptome sequencing technology, and the expression of several highly deregulated mRNAs, including Frs3, Zfp52, Dnajc6, Nedd4l, Tep1, Myef2, Tgfbr1, Fgf12, Mef2c, Tfdp1 and lncRNA, including ENSRNOT00000080713, ENSRNOT00000090564, ENSRNOT00000082588, ENSRNOT00000091080, ENSRNOT00000091570, ENSRNOT00000087777, ENSRNOT00000082061, ENSRNOT00000091108, ENSRNOT00000087028, ENSRNOT00000086475, were further validated via reverse transcription-quantitative PCR. The number of altered expressed lncRNAs was 126, among which there were 41 upregulated probe sets and 85 downregulated sets. A total of 470 mRNAs were differentially expressed, in which 231 probe sets were upregulated and 239 were downregulated. Gene Ontology analysis indicated that dysregulated transcripts related to biological processes were mainly associated with 'cell-cell signaling'. Moreover, pathway analysis demonstrated significant changes in the 'PI3K/Akt signaling pathway' and the 'p53 signaling pathway'. Thus, the altered expression of lncRNAs in the spinal cord may be of considerable importance in the process of MIRI. The present results could provide an insight into the potential roles and mechanism of lncRNAs during the early stage of reperfusion.

摘要

心肌缺血再灌注损伤(MIRI)是临床心脏病学中的一个重要问题,指的是与血管阻塞所致损伤相比,心肌缺血一段时间后血液再灌注所引起的更严重的心肌损伤。脊髓作为心脏感觉和交感神经纤维的主要传入和传出中心,近年来在MIRI的调控方面受到了越来越多的关注。以往研究表明,MIRI与心肌中长链非编码(lnc)RNA的异常表达密切相关;然而,关于MIRI后脊髓中lncRNA表达改变的影响的报道有限。为了研究MIRI后脊髓中lncRNA的表达模式及其在再灌注早期的潜在作用,在大鼠中建立了MIRI模型。心肌缺血30分钟和再灌注2小时后,立即解剖并分离上胸段脊髓组织。使用转录组测序技术筛选脊髓组织中的lncRNA和mRNA,并通过逆转录定量PCR进一步验证包括Frs3、Zfp52、Dnajc6、Nedd4l、Tep1、Myef2、Tgfbr1、Fgf12、Mef2c、Tfdp1等几种高度失调的mRNA以及包括ENSRNOT00000080713、ENSRNOT00000090564、ENSRNOT00000082588、ENSRNOT00000091080、ENSRNOT00000091570、ENSRNOT00000087777、ENSRNOT00000082061、ENSRNOT00000091108、ENSRNOT00000087028、ENSRNOT00000086475等lncRNA的表达。表达改变的lncRNA数量为126个,其中上调的探针集有41个,下调的有85个。共有470个mRNA差异表达,其中上调的探针集有231个,下调的有239个。基因本体分析表明,与生物过程相关的失调转录本主要与“细胞间信号传导”有关。此外,通路分析显示“PI3K/Akt信号通路”和“p53信号通路”有显著变化。因此,脊髓中lncRNA的表达改变可能在MIRI过程中具有相当重要的意义。目前的结果可以为lncRNA在再灌注早期的潜在作用和机制提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/264a/7903382/2d5cde0c0421/etm-21-04-09783-g00.jpg

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