Lu Wen-Jing, Zeng Li-Li, Wang Yang, Zhang Yu, Liang Huai-Bin, Tu Xuan-Qiang, He Ji-Rong, Yang Guo-Yuan
Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
Curr Neurovasc Res. 2018;15(1):63-71. doi: 10.2174/1567202615666180319143509.
This study aims to explore the function of blood microRNA-15a (miR-15a) in the pathogenesis of acute cerebral ischemia (AIS).
Blood samples were collected from healthy control and AIS patients within 72 h after onset. A model of ischemia in human umbilical vein endothelial cells (HUVECs) was established through oxygen and glucose deprivation (OGD). MiR-15a in patients and in cells was measured using real-time quantitative polymerase chain reaction (qPCR). The predicted target of miR-15a such as interleukin-6 (IL-6) and insulin-like growth factors-1 (IGF-1) in plasma was detected by enzyme-linked immunosorbent assay (ELISA). The relations between blood miR-15a and stroke severity, stroke etiology, infarct location, stroke prognosis, predicted targets were analyzed by Statistical Product and Service Solutions (SPSS) software respectively.
Higher miR-15a levels were found in AIS patients and ischemic cells within 72 h, compared to control (p < 0.05). Receiver Operating Characteristic (ROC) analysis showed that blood miR-15a predicted stroke onset with 98.67% specificity. Blood miR-15a had a negative correlation with National Institutes of Health Stroke Scale (NIHSS) scores (r = -0.3695, p < 0.01). The AIS patients with increased miR-15a levels had a better prognosis. MiR-15a was up-regulated in anterior circulation infarction and small-artery atherosclerosis stroke. Plasma levels of IL-6 and IGF-1 were associated with blood miR-15a (r = -0.6051, 0.3231, p < 0.05, respectively).
Blood miR-15a associates with IL-6, IGF-1 and acute cerebral ischemia. It could serve as a potential diagnostic biomarker and therapeutic target for stroke.
本研究旨在探讨血液微小RNA-15a(miR-15a)在急性脑缺血(AIS)发病机制中的作用。
在发病后72小时内采集健康对照者和AIS患者的血液样本。通过氧糖剥夺(OGD)建立人脐静脉内皮细胞(HUVECs)缺血模型。采用实时定量聚合酶链反应(qPCR)检测患者和细胞中的miR-15a。通过酶联免疫吸附测定(ELISA)检测血浆中miR-15a的预测靶点,如白细胞介素-6(IL-6)和胰岛素样生长因子-1(IGF-1)。分别使用统计产品与服务解决方案(SPSS)软件分析血液miR-15a与卒中严重程度、卒中病因、梗死部位、卒中预后、预测靶点之间的关系。
与对照组相比,AIS患者和缺血细胞在72小时内的miR-15a水平更高(p<0.05)。受试者工作特征(ROC)分析表明,血液miR-15a预测卒中发作的特异性为98.67%。血液miR-15a与美国国立卫生研究院卒中量表(NIHSS)评分呈负相关(r = -0.3695,p<0.01)。miR-15a水平升高的AIS患者预后较好。miR-15a在前循环梗死和小动脉粥样硬化性卒中中上调。血浆IL-6和IGF-1水平与血液miR-15a相关(r分别为-0.6051、0.3231,p<0.05)。
血液miR-15a与IL-6、IGF-1和急性脑缺血相关。它可作为卒中潜在的诊断生物标志物和治疗靶点。