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循环微小RNA表达谱:慢性神经损伤的一种新型潜在预测指标。

Circulating microRNA expression profile: a novel potential predictor for chronic nervous lesions.

作者信息

Xu Yongming, Zhang Xin, Pu Shaofeng, Wu Junzhen, Lv Yingying, Du Dongping

机构信息

Pain Management Center and Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.

Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2014 Nov;46(11):942-9. doi: 10.1093/abbs/gmu090. Epub 2014 Sep 30.

Abstract

The mechanisms of chronic neuropathic pain are not clear. Serum microRNAs (miRNAs) might show a special feature for chronic nervous lesions. However, little is known about the changes in circulating miRNAs for the neuropathic pain. Therefore, changes in the circulating miRNAs expression profile for the neuropathic pain were investigated. Serum was collected from rats before and after spinal nerve ligation (SNL) surgery, and a microarray analysis was performed to determine the changes in miRNA expression profile. The expression of inflammatory cytokines in serum from the same individuals, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), was also measured. The results showed that the expression levels of IL-6, TNF-α, and MCP-1 were significantly elevated in SNL rats which were significantly correlated with pain levels. Nine miRNAs with significantly different expression levels before and after SNL surgery were identified by microarray analysis, which were further validated by quantitative real-time polymerase chain reaction analyses. Compared with naive rats without SNL surgery, the expression of five miRNAs (hsa-miR-221, hsa-miR-34c, hsa-miR-21, hsa-miR-30a-5p, and hsa-miR-206) in the serum of rats after SNL surgery was decreased and four miRNAs (hsa-miR-31-5p, hsa-miR-133b, hsa-miR-22, and hsa-miRPlus-A1087) were increased, suggesting that miRNA changes may involve in the regulation of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs, and the results showed that the transcripts with multiple predicted target sites belonged to neurologically important pathways. Bioinformatics analysis revealed that several target genes are related to the activation of cell signaling associated with nervous lesions. In this study, the changes to miRNA profiles in serum under neuropathic pain conditions were shown for the first time, suggesting that circulating miRNAs profile in serum is a potential predictor for neuropathic pain.

摘要

慢性神经性疼痛的机制尚不清楚。血清微小RNA(miRNA)可能对慢性神经损伤具有特殊特征。然而,关于神经性疼痛患者循环miRNA的变化知之甚少。因此,研究了神经性疼痛患者循环miRNA表达谱的变化。在大鼠脊髓神经结扎(SNL)手术前后采集血清,并进行微阵列分析以确定miRNA表达谱的变化。还测量了同一受试者血清中炎症细胞因子的表达,包括白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)和单核细胞趋化蛋白-1(MCP-1)。结果显示,SNL大鼠中IL-6、TNF-α和MCP-1的表达水平显著升高,且与疼痛程度显著相关。通过微阵列分析鉴定出SNL手术前后表达水平有显著差异的9种miRNA,并通过定量实时聚合酶链反应分析进一步验证。与未进行SNL手术的正常大鼠相比,SNL手术后大鼠血清中5种miRNA(hsa-miR-221、hsa-miR-34c、hsa-miR-21、hsa-miR-30a-5p和hsa-miR-206)的表达降低,4种miRNA(hsa-miR-31-5p、hsa-miR-133b、hsa-miR-22和hsa-miRPlus-A1087)的表达升高,提示miRNA变化可能参与神经性疼痛的调节。使用TargetScan预测这些miRNA的mRNA靶标,结果显示具有多个预测靶位点的转录本属于神经学上重要的途径。生物信息学分析表明,几个靶基因与神经损伤相关的细胞信号激活有关。本研究首次展示了神经性疼痛条件下血清中miRNA谱的变化,提示血清中循环miRNA谱是神经性疼痛的潜在预测指标。

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