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缺血预处理和后处理对大鼠肝脏在缺血/再灌注后基因表达谱有显著影响。

Ischemic pre- and postconditioning has pronounced effects on gene expression profiles in the rat liver after ischemia/reperfusion.

机构信息

Department of Surgical Gastroenterology L, Aarhus University Hospital, Denmark.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2012 Aug 15;303(4):G482-9. doi: 10.1152/ajpgi.00337.2011. Epub 2012 Jun 7.

Abstract

Ischemic pre (IPC)- and postconditioning (IPO) protect the liver against ischemia/reperfusion injuries (IRI). Conditioning involves several different trigger factors, mediators, and effectors, many of which are affected during the early phase of reperfusion, ultimately resulting in decreased liver injuries. The aim of the present study was to investigate the genomic response induced by IPC and IPO in ischemia/reperfusion-damaged rat liver biopsies. Forty-eight male Wistar rats were divided into five groups: sham (n = 8), IRI (n = 10), IPC (n = 10), IPO (n = 10), and IPC + IPO (n = 10). The rat livers were subjected to 30 min of ischemia. Liver biopsies and blood samples were taken after 30 min of reperfusion. The biopsies were analyzed using cDNA microarrays with validation by quantitative RT-PCR. The significance analysis of microarray was used to identify genes with changed expression levels. A comparison analysis of the intervention groups showed a highly increased number of genes, with significantly different expression in the conditioned groups compared with the IRI group. A total of 172 genes were identified as the most highly affected, and these genes showed similar patterns with regard to the up- and downregulated expression levels within the conditioned groups. Pathway analysis of the 172 genes identified four networks that were involved in increased gene expression, cellular growth, and proliferation. In conclusion, the present study demonstrated that IPC, IPO, and IPC + IPO had pronounced effects on the expression levels of a large number of genes during early reperfusion. IPC, IPO, and IPC + IPO seem to mediate their protective effects by regulating the same genes and genetic networks. These identified networks are known to be involved in maintaining cellular homeostasis.

摘要

缺血预处理(IPC)和后处理(IPO)可保护肝脏免受缺血/再灌注损伤(IRI)。预处理涉及几种不同的触发因素、介质和效应物,其中许多在再灌注的早期阶段受到影响,最终导致肝损伤减少。本研究旨在研究 IPC 和 IPO 诱导的缺血/再灌注损伤大鼠肝活检的基因组反应。将 48 只雄性 Wistar 大鼠分为五组:假手术组(n = 8)、IRI 组(n = 10)、IPC 组(n = 10)、IPO 组(n = 10)和 IPC + IPO 组(n = 10)。大鼠肝脏缺血 30 分钟。再灌注 30 分钟后采集肝活检和血样。使用 cDNA 微阵列分析活检,并通过定量 RT-PCR 进行验证。微阵列的意义分析用于鉴定表达水平发生变化的基因。干预组的比较分析显示,具有显著不同表达的基因数量显著增加。共有 172 个基因被确定为受影响最大的基因,这些基因在预处理组中的上调和下调表达水平具有相似的模式。对 172 个基因的通路分析确定了四个涉及基因表达增加、细胞生长和增殖的网络。总之,本研究表明,IPC、IPO 和 IPC + IPO 在再灌注早期对大量基因的表达水平有明显影响。IPC、IPO 和 IPC + IPO 似乎通过调节相同的基因和遗传网络来介导其保护作用。这些鉴定的网络已知参与维持细胞内稳态。

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