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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81771622, 81401245]
第一作者单位：[1]Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
通讯作者：
通讯机构：[1]Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China[*1]Department of Pediatrics, Beijing Friendship Hospital,Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050,China.
推荐引用方式(GB/T 7714)：
Zhang Nan,Yang Lijun,Meng Lanlan,et al.Inhibition of miR-200b-3p alleviates hypoxia-ischemic brain damage via targeting Slit2 in neonatal rats[J].BIOCHEMICAL and BIOPHYSICAL RESEARCH COMMUNICATIONS.2020,523(4):931-938.doi:10.1016/j.bbrc.2020.01.029.
APA：
Zhang, Nan,Yang, Lijun,Meng, Lanlan&Cui, Hong.(2020).Inhibition of miR-200b-3p alleviates hypoxia-ischemic brain damage via targeting Slit2 in neonatal rats.BIOCHEMICAL and BIOPHYSICAL RESEARCH COMMUNICATIONS,523,(4)
MLA：
Zhang, Nan,et al."Inhibition of miR-200b-3p alleviates hypoxia-ischemic brain damage via targeting Slit2 in neonatal rats".BIOCHEMICAL and BIOPHYSICAL RESEARCH COMMUNICATIONS 523..4(2020):931-938
