Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Biochem Biophys Res Commun. 2020 Mar 19;523(4):931-938. doi: 10.1016/j.bbrc.2020.01.029. Epub 2020 Jan 18.
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.
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.
Our study has demonstrated that Slit2 is a target gene of miR-200b-3p and that the hypoxia-ischemic 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.
早产儿脑损伤常因缺氧缺血而发生于极低出生体重儿（VLBW），可导致认知障碍和运动障碍。许多 miRNA 已被证明参与缺氧缺血性脑损伤（HIBD）。本研究旨在探讨 miR-200b-3p 在缺氧缺血性脑损伤新生大鼠脑损伤中的作用。
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 显示，缺氧缺血处理后大鼠脑内 miR-200b-3p 早期上调。生物信息学分析表明 Slit2 是 miR-200b-3p 的靶基因，荧光素酶报告基因实验证实 miR-200b-3p 可与 Slit2 mRNA 相互作用并靶向其。miR-200b-3p 拮抗剂抑制 miR-200b-3p 可增加大鼠脑内 Slit2 mRNA 和蛋白表达。TUNEL 检测和透射电镜（TEM）分析显示，miR-200b-3p 拮抗剂给药可减少缺氧缺血处理后大鼠神经元凋亡数量。与对照组相比，miR-200b-3p 拮抗剂给药可减轻缺氧缺血诱导的动物空间和学习记忆丧失。
本研究表明 Slit2 是 miR-200b-3p 的靶基因，通过抑制 miR-200b-3p 可减轻新生大鼠缺氧缺血性脑损伤，miR-200b-3p 可能是 HIBD 的潜在治疗靶点，值得进一步研究。
