循环中miR-223和胰岛素样生长因子-1的增加与患者急性缺血性卒中的发病机制相关。
Increase of circulating miR-223 and insulin-like growth factor-1 is associated with the pathogenesis of acute ischemic stroke in patients.
作者信息
Wang Yang, Zhang Yu, Huang Jun, Chen Xiaoyan, Gu Xiang, Wang Yongting, Zeng Lili, Yang Guo-Yuan
机构信息
Department of neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, 200025 Shanghai, China.
出版信息
BMC Neurol. 2014 Apr 8;14:77. doi: 10.1186/1471-2377-14-77.
BACKGROUND
The relationship between circulating microRNA-223 and pathogenesis of acute ischemic stroke is unknown. Here we investigated the roles and possible targets of circulating microRNA-223 in human ischemic stroke within the first 72 hours.
METHODS
Blood samples were collected from patients within 72 hours after cerebral ischemia (n = 79) and compared with healthy control samples (n = 75). The level of possible downstream factors of microRNA-223 including insulin-like growth factor-1, insulin-like growth factor-1 receptor and interleukin-6 was examined by ELISA assay. The relationship between the microRNA-223 level and NIHSS scores, TOAST subtypes, and infarct volume was analyzed respectively. In addition, twelve adult male CD-1 mice underwent middle cerebral artery occlusion using the suture technique. Circulating blood and brain tissue in the ischemic ipsilateral hemisphere were collected at 24 hours after middle cerebral artery occlusion. microRNA-223 was detected by real-time polymerase chain reactions.
RESULTS
microRNA-223 levels in the circulating blood of acute ischemic stroke patients were greatly increased compared to the control (p < 0.05). microRNA-223, which were negatively correlated with NIHSS scores (r = -0.531, p < 0.01) and infarct volume (r = -0.265, p = 0.039), was significantly up-regulated in large artery and small artery strokes. The plasma level of insulin-like growth factor-1 was positively associated with that of microRNA-223 (r = 0.205, p = 0.022). Moreover, microRNA-223 in blood and brain were positively correlated (r = 0.834, p < 0.05), and they were up-regulated significantly in mice that underwent middle cerebral artery occlusion (p < 0.05).
CONCLUSIONS
Our results suggest that microRNA-223 is associated with acute ischemic stroke and possibly plays a role in stroke through up-regulating growth factor such as insulin-like growth factor-1 gene.
背景
循环中的微小RNA-223与急性缺血性中风发病机制之间的关系尚不清楚。在此，我们研究了循环微小RNA-223在人类缺血性中风发病72小时内的作用及可能的靶点。
方法
收集脑缺血后72小时内患者的血样（n = 79），并与健康对照样本（n = 75）进行比较。通过酶联免疫吸附测定法检测微小RNA-223可能的下游因子，包括胰岛素样生长因子-1、胰岛素样生长因子-1受体和白细胞介素-6的水平。分别分析微小RNA-223水平与美国国立卫生研究院卒中量表（NIHSS）评分、急性卒中治疗Org 10172（TOAST）亚型及梗死体积之间的关系。此外，12只成年雄性CD-1小鼠采用缝合技术进行大脑中动脉闭塞。大脑中动脉闭塞24小时后收集缺血同侧半球的循环血液和脑组织。通过实时聚合酶链反应检测微小RNA-223。
结果
与对照组相比，急性缺血性中风患者循环血液中微小RNA-223水平显著升高（p < 0.05）。微小RNA-223与NIHSS评分（r = -0.531，p < 0.01）和梗死体积（r = -0.265，p = 0.039）呈负相关，在大动脉和小动脉卒中中显著上调。胰岛素样生长因子-1的血浆水平与微小RNA-223呈正相关（r = 0.205，p = 0.022）。此外，血液和脑组织中的微小RNA-223呈正相关（r = 0.834，p < 0.05），在大脑中动脉闭塞的小鼠中显著上调（p < 0.05）。
结论
我们的结果表明，微小RNA-223与急性缺血性中风相关，可能通过上调胰岛素样生长因子-1基因等生长因子在中风中发挥作用。
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