Diagnostic and Immunosuppressive Potential of Elevated Mir-424 Levels in Circulating Immune Cells of Ischemic Stroke Patients.
Diagnostic and Immunosuppressive Potential of Elevated Mir-424 Levels in Circulating Immune Cells of Ischemic Stroke Patients.
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缺血性中风患者循环免疫细胞中 Mir-424 水平升高的诊断和免疫抑制潜力。
DOI：
10.14336/ad.2017.0602
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发表时间：
2018-04
影响因子：
7.4
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Li G;Ma Q;Wang R;Fan Z;Tao Z;Liu P;Zhao H;Luo Y
我们先前的研究表明，microRNA-424（miR-424）通过靶向细胞周期蛋白抑制小胶质细胞增殖和激活来保护实验性中风。本研究旨在进一步探讨miR-424在急性缺血性脑卒中（AIS）患者外周血免疫细胞中的临床意义。从40名症状发作6小时内的患者和27名对照受试者中采集血液样本。通过定量实时PCR测定淋巴细胞、中性粒细胞和血浆中的miR-424水平。采用受试者工作特征（ROC）曲线评价miR-424对脑卒中诊断的敏感性和特异性。使用Pearson相关性检验分析miR-424水平与临床数据之间的相关性。ELISA法检测血浆TNF-α、IL-10和IGF-1水平。值得注意的是，淋巴细胞和中性粒细胞中的miR-424表达水平在卒中后增加，提示其在缺血性卒中中的诊断价值。中性粒细胞中的miR-424水平与梗死体积呈负相关。淋巴细胞miR-424水平与淋巴细胞数量和细胞周期蛋白依赖性激酶CDK 6表达呈负相关。此外，在卒中患者中，血浆TNF-α和IGF-1水平分别升高和降低，淋巴细胞和中性粒细胞中的miR-424水平均与血浆TNF-α、IL-10或IGF-1水平呈负相关。总之，外周免疫细胞中的miR-424水平具有诊断缺血性卒中的潜力，并且可能通过抑制淋巴细胞中CDK 6依赖性途径或中性粒细胞中CDK 6非依赖性途径的外周炎症反应来影响急性卒中的严重程度。
Our previous study demonstrated that microRNA-424 (miR-424) protected against experimental stroke through inhibition of microglial proliferation and activation by targeting cell cycle proteins. The purpose of this study was to further explore the clinical significance of miR-424 in peripheral immune cells of patients with acute ischemic stroke (AIS). Blood samples were collected from 40 patients within 6 hours of symptom onset and 27 control subjects. MiR-424 levels in lymphocytes, neutrophils and plasma were determined by quantitative realtime-PCR. The diagnostic sensitivity and specificity of miR-424 for stroke was evaluated by receiver operator characteristic (ROC) curve. The correlation between miR-424 levels and clinical data was analyzed using Pearson’s correlation test. Plasma levels of inflammatory mediators (TNF-α, IL-10) and neurotrophic factor (IGF-1) were detected by ELISA. Notably, miR-424 expression levels in lymphocytes and neutrophils increased after stroke, suggestive of its diagnostic value in ischemic stroke. MiR-424 levels in neutrophils were negatively correlated with infarct volume. Lymphocytic miR-424 levels were negatively correlated with the number of lymphocytes and the expression of cyclin-dependent kinase CDK6. Moreover, plasma TNF-α and IGF-1 levels increased and decreased, respectively, in stroke patients, and miR-424 levels in lymphocytes and neutrophils were both inversely correlated with plasma TNF-α, IL-10, or IGF-1 levels. In summary, miR-424 levels in peripheral immune cells has diagnostic potential for ischemic stroke, and might affect the severity of acute stroke by depressing the peripheral inflammatory response through CDK6-dependent pathway in lymphocytes or CDK6-independent pathway neutrophils.