Potential Neuroprotective Effect of miR-451 Against Cerebral Ischemia/Reperfusion Injury in Stroke Patients and a Mouse Model
Potential Neuroprotective Effect of miR-451 Against Cerebral Ischemia/Reperfusion Injury in Stroke Patients and a Mouse Model
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DOI：
10.1016/j.wneu.2019.05.194
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发表时间：
2019-10-01
影响因子：
2
通讯作者：
Zhao, Jiannong
中科院分区：
文献类型：
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作者：
Fu, Chuanyi;Chen, Shuijie;Zhao, Jiannong
目的：最近，据报道 microRNA (miR) 是缺血性中风的新型调节因子。在这项研究中，我们研究了 miR-451 的表达模式及其在人类缺血性中风和体内小鼠模型中的临床应用。方法：评估了缺血性中风后患者和小鼠中 miR-451 的水平。对美国国立卫生研究院中风量表评分和脑梗塞体积进行分析，以了解 miR-451 表达与临床信息的相关性。此外，由12只成年雄性小鼠建立的大脑中动脉闭塞模型，在大脑中动脉闭塞后24小时采集血液样本和脑组织。结果：结果显示，缺血性脑卒中患者循环血中miR-451水平较对照组大幅降低。进一步的相关性分析显示，miR-451与美国国立卫生研究院卒中量表评分（r = -0.6104，P < 0.001）和梗塞体积（r = -0.5442，P < 0.001）之间呈负相关。此外，在体内大脑中动脉闭塞时，miR-451 下调，并且大脑和血液中的 miR-451 之间呈负相关（r = 0.9240，P < 0.01）。此外，miR-451的强制表达减弱了局灶性缺血性中风小鼠的缺血性脑梗死和细胞凋亡水平，而miR-451的下调则显着增强了缺血性损伤。 结论：总而言之，miR-451在缺血性中风中显示出神经保护作用，并可能作为缺血性中风的新治疗靶点。
OBJECTIVE: Recently, microRNAs (miRs) have been reported to be novel regulators in ischemic stroke. In this study, we investigated the pattern of miR-451 expression along with its clinical application in human ischemic stroke and in an in vivo mouse model.METHODS: The level of miR-451 was evaluated in patients and mice after ischemic stroke. National Institute of Health Stroke Scale scores and brain infarct volume were analyzed to the correlation of miR-451 expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion model consisting of 12 adult male mice at 24 hours after the middle cerebral artery occlusion.RESULTS: The results showed that miR-451 levels in the circulating blood of ischemic stroke patients were greatly decreased compared with the control. Further correlation analysis revealed a negative association between miR-451 and National Institute of Health Stroke Scale scores (r = -0.6104, P < 0.001) and infarct volume (r = -0.5442, P < 0.001). Moreover, miR-451 was downregulated in response to middle cerebral artery occlusion in vivo, along with a negative correlation between miR-451 in brain and blood (r = 0.9240, P < 0.01). In addition, forced expression of miR-451 weakened ischemic brain infarction and apoptosis levels in focal ischemia-stroked mice, while downregulation of miR-451 significantly augmented ischemic injury.CONCLUSIONS: In conclusion, miR-451 displays the neuroprotective effect in ischemic stroke and might serve as a novel therapeutic target of ischemic stroke.