Yu Lei, Gu Tianxiang, Shi Enyi, Wang Yongchao, Fang Qin, Wang Chun
Department of cardiac surgery, the first affiliated hospital of China Medical University, Shenyang, China.
Department of cardiac surgery, the first affiliated hospital of China Medical University, Shenyang, China
Eur J Cardiothorac Surg. 2016 Jun;49(6):1725-31. doi: 10.1093/ejcts/ezv460. Epub 2016 Jan 21.
Acute kidney injury (AKI) is a severe complication of cardiopulmonary bypass-deep hypothermic circulatory arrest (DHCA) surgery. Non-coding microRNAs (miRNAs) are considered as key players in kidney physiology and pathology. However, whether they are implicated in DHCA-induced AKI at the early stage post-surgery is less studied, and requires for further investigation.
In this study, kidney tissues were removed at 2 h post-surgery from Sprague-Dawley rats that underwent a 60-min DHCA (18°C), with samples from sham-operated rats as control. Renal RNA isolates were analysed with Affymetrix miRNA microarray 4.0 containing 728 mature rat miRNA probes.
Seventy-one miRNAs were down-regulated and 4 were up-regulated in the kidneys of DHCA rats [log2 (fold change, FC) > 1, P < 0.05]. Novel differentially expressed miRNAs, such as miRNA-3068, miR-1949 and miR-3473, were identified in the injured kidney tissues. Putative target genes of the down-regulated miR-30b-5p, miR-199a-5p, miR-148b-3p and miR-10a-3p were subjected to analyses of gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results indicated that these miRNAs targeted a large set of genes involved in essential biological processes related to AKI pathogenesis, such as apoptotic process and response to hypoxia, as well as genes implicated in critical signalling pathways, such as chemokine, lysosome and FoxO signalling pathways (false discovery rate-corrected, P < 0.05).
The identified 75 differentially expressed miRNAs hold the potential to serve as novel early markers and novel therapeutic targets for DHCA-AKI.
急性肾损伤（AKI）是体外循环 - 深低温停循环（DHCA）手术的严重并发症。非编码微小RNA（miRNA）被认为是肾脏生理和病理过程中的关键因素。然而，它们是否在手术后早期参与DHCA诱导的AKI尚鲜少研究，需要进一步探究。
在本研究中，于手术后2小时从接受60分钟DHCA（18°C）的Sprague-Dawley大鼠身上取出肾脏组织，以假手术大鼠的样本作为对照。使用含有728个成熟大鼠miRNA探针的Affymetrix miRNA微阵列4.0对肾脏RNA分离物进行分析。
在DHCA大鼠的肾脏中，71种miRNA表达下调，4种miRNA表达上调[log2（倍数变化，FC）> 1，P < 0.05]。在受损的肾脏组织中鉴定出了新的差异表达miRNA，如miRNA - 3068、miR - 1949和miR - 3473。对下调的miR - 30b - 5p、miR - 199a - 5p、miR - 148b - 3p和miR - 10a - 3p的推定靶基因进行基因本体论（GO）类别和京都基因与基因组百科全书（KEGG）通路分析。结果表明，这些miRNA靶向大量参与与AKI发病机制相关的基本生物学过程的基因，如凋亡过程和对缺氧的反应，以及涉及关键信号通路的基因，如趋化因子、溶酶体和FoxO信号通路（错误发现率校正，P < 0.05）。
鉴定出的75种差异表达miRNA有潜力作为DHCA - AKI的新型早期标志物和新型治疗靶点。
