Inhibition of miR-200b-3p alleviates hypoxia-ischemic brain damage via targeting Slit2 in neonatal rats
Inhibition of miR-200b-3p alleviates hypoxia-ischemic brain damage via targeting Slit2 in neonatal rats
复制标题
抑制 miR-200b-3p 通过靶向 Slit2 减轻新生大鼠缺氧缺血性脑损伤
DOI：
10.1016/j.bbrc.2020.01.029
复制
发表时间：
2020-03-19
影响因子：
3.1
通讯作者：
Cui, Hong
中科院分区：
文献类型：
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作者：
Zhang, Nan;Yang, Lijun;Cui, Hong
背景资料：早产儿的脑损伤通常发生在极低出生体重儿（VLBW）中，这是由于缺氧缺血，并可导致认知障碍和运动障碍。许多miRNAs已被证实参与缺氧缺血性脑损伤（hypoxia-ischemic brain damage，HIBD）。本研究旨在探讨miR-200 b-3 p在新生大鼠缺氧缺血性脑损伤中的作用。方法：采用3日龄SD大鼠建立模拟早产儿缺氧缺血性脑损伤模型。RT-qPCR结果显示，缺氧缺血处理后早期大鼠脑组织中miR-200 b-3 p表达上调。生物信息学分析证实Slit 2是miR-200 b-3 p的靶基因，荧光素酶报告基因分析证实miR-200 b-3 p可与Slit 2 mRNA相互作用并靶向Slit 2 mRNA。在大鼠脑中，通过Escheromir抑制miR-200 b-3 p在mRNA和蛋白水平上增加Slit 2表达。TUNEL分析和透射电子显微镜（TEM）分析显示，由于给予miR-200 b-3 p阿托洛尔，缺氧缺血处理的动物中凋亡神经元的数量减少。结论：我们的研究证实了Slit 2是miR-200 b-3 p的靶基因，通过Slit 2抑制miR-200 b-3 p可以减轻新生大鼠缺氧缺血性脑损伤。miR-200 b-3 p可能是HIBD潜在的治疗靶点。(C)2020爱思唯尔公司All rights reserved.
Background: Brain damage in premature infants often occurs in very low birth weight infants (VLBW) as a result of hypoxia-ischemia and can lead to cognitive impairment and movement disorders. Many miRNAs have been demonstrated to participate in hypoxia-ischemic brain damage (HIBD). This study was designed to investigate the roles of miR-200b-3p in brain damage of neonatal rats induced by hypoxia-ischemia.Methods and results: Three-day-old SD rats were used to establish the model of hypoxia-ischemic brain injury mimicking premature infants. RT-qPCR showed that miR-200b-3p was up-regulated in rat brains at the early stage following hypoxia-ischemic treatment. Bioinformatics analysis identified that Slit2 is a target gene of miR-200b-3p and luciferase reporter gene assay confirmed that miR-200b-3p can interact with and target Slit2 mRNA. Inhibition of miR-200b-3p by antagomir increased Slit2 expression at both the mRNA and protein levels in rat brains. TUNEL assay and transmission electron microscopy (TEM) analysis showed decreased numbers of apoptotic neurons in the hypoxia-ischemia-treated animals as a result of administration of miR-200b-3p antagomir. Administration of miR-200b-3p antagomir attenuated spatial and learning memory loss in the animals induced by hypoxia-ischemia as compared to controls.Conclusion: Our study has demonstrated that Slit2 is a target gene of miR-200b-3p and that the hypoxiaischemic brain damage in neonatal rats was alleviated by inhibiting miR-200b-3p via Slit2. miR-200b-3p may be a potential therapeutic target of HIBD for further investigation. (C) 2020 Elsevier Inc. All rights reserved.