Association of Altered Serum MicroRNAs with Perihematomal Edema after Acute Intracerebral Hemorrhage.
Association of Altered Serum MicroRNAs with Perihematomal Edema after Acute Intracerebral Hemorrhage.
复制标题
血清微小RNA改变与急性脑出血后血肿周围水肿的关系
DOI：
10.1371/journal.pone.0133783
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tang L
中科院分区：
文献类型：
--
作者：
Zhu Y;Wang JL;He ZY;Jin F;Tang L
背景与目的脑出血(ICH)后，血肿周围水肿(Phe)可导致继发性脑损伤，加重患者预后。MicroRNAs(MiRNAs)在循环中是稳定的，其独特的表达谱在调节血管疾病方面具有基础作用。这项研究的目的是验证这一假设，即改变miRNA水平与脑出血患者的PHE有关。方法对脑出血患者入院时及随访的CT扫描中的血肿和PHE体积进行测量。用Exiqon miRCURY LNA芯片检测脑出血患者和健康对照组的全基因组miRNA图谱，并用定量逆转录聚合酶链式反应(qRT-PCR)进行验证。生物信息学分析研究了失调的miRNA靶基因和涉及的信号通路。结果我们发现55个miRNAs在脑出血患者与正常对照组之间存在差异表达，其中54个下调，1个上调。定量RT-PCR证实，与对照组相比，脑出血患者miR-126(0.63倍)、miR-146a(0.64倍)、miR-let-7a(0.50倍)和miR-26a(0.54倍)减少。脑出血患者血清miR-126、miR-146a、miR-let-7a和miR-26a水平与第3-4天的相对Phe显著相关(r=−0.714；P<；0.001)。结论脑出血患者的miRNA表达谱具有特异性。MiR-126低表达与PHE程度呈正相关，提示miR-126可能在脑出血后PHE的发生发展中起一定的致病作用。
Background and Purpose Perihematomal edema (PHE) contributes to secondary brain damage and aggravates patient outcomes after intracerebral hemorrhage (ICH). MicroRNAs (miRNAs) are stable in circulation, and their unique expression profiles have fundamental roles in modulating vascular disease. The objective of this study was to test the hypothesis that altered miRNA levels are associated with PHE in ICH patients. Methods Hematoma and PHE volumes of ICH patients were measured on admission and in follow-up computed tomography scans. Whole-genome miRNA profiles of ICH patients and healthy controls were determined using the Exiqon miRCURY LNA Array, and validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatics analysis investigated dysregulated miRNA target genes and the signaling pathways involved. Results We identified 55 miRNAs that were differentially expressed in ICH patients compared with normal controls, of which 54 were down-regulated and one was up-regulated. qRT-PCR confirmation showed decreases in miR-126 (0.63-fold), miR-146a (0.64-fold), miR-let-7a (0.50-fold), and miR-26a (0.54-fold) in ICH patients relative to controls. Serum miR-126, but not miR-146a, miR-let-7a or miR-26a, levels were significantly correlated with relative PHE volume on days 3–4 (r = −0.714; P<0.001) in patients with ICH. Conclusions ICH patients appear to have a specific miRNA expression profile. Low expression of miR-126 was positively correlated with the extent of PHE, suggesting it may have a pathogenic role in the development of PHE after ICH.