Perinatal hypoxic ischemia encephalopathy (HIE) is a serious disease occurring in neonate. Growing studies have already validated the pivotal function of microRNAs (miRNAs) in a variety of diseases. However, whether miR-130a-3p participated in neonatal HIE remains vague. In this study, we planned to explore the molecular mechanism of H19/miR-130a-3p/DAPK1 axis in HIE. We established a in vivo mice model induced by middle cerebral artery occlusion/reperfusion (MCAO/R) and in vitro models of SH-SY5Y and N2a cells following oxygen-glucose deprivation and reperfusion (OGD/R) treatment. DAPK1 is widely explored in multiple diseases and bioinformatic analysis indicated miR-130a-3p potentially targeted DAPK1. We found DAPK1 expression was upregulated while miR-130a-3p expression was downregulated in HIE, MCAO/R mice model and OGD/R treated SH-SY5Y and N2a cells. Moreover, miR-130a-3p was verified to target DAPK1. DAPK1 upregulation restored the inhibitory effect of miR-130a-3p elevation on SH-SY5Y and N2a cells apoptosis as well as on cerebral damage by I/R. In addition, H19 was confirmed to bind with miR-130a-3p in SH-SY5Y and N2a cells. H19 and miR-130a-3p coordinately regulated SH-SY5Y and N2a cells apoptosis as well as cerebral damage by I/R. In conclusion, H19/miR-130a-3p/DAPK1 axis regulated the pathophysiology of neonatal HIE, suggesting potential therapeutic targets for neonatal HIE treatment.

中文翻译：

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H19/miR-130a-3p/DAPK1轴调控新生儿缺氧缺血性脑病的病理生理

围产期缺氧缺血性脑病（HIE）是一种严重的新生儿疾病。越来越多的研究已经验证了 microRNA (miRNA) 在多种疾病中的关键功能。然而，miR-130a-3p 是否参与新生儿 HIE 仍不清楚。在本研究中，我们计划探索H19/miR-130a-3p/DAPK1轴在HIE中的分子机制。我们建立了大脑中动脉闭塞/再灌注（MCAO/R）诱导的体内小鼠模型和氧糖剥夺再灌注（OGD/R）治疗后SH-SY5Y和N2a细胞的体外模型。DAPK1 在多种疾病中得到广泛探索，生物信息学分析表明 miR-130a-3p 可能靶向 DAPK1。我们发现 DAPK1 表达上调而 miR-130a-3p 表达在 HIE 中下调，MCAO/R 小鼠模型和 OGD/R 处理的 SH-SY5Y 和 N2a 细胞。此外，证实了 miR-130a-3p 靶向 DAPK1。DAPK1 上调恢复了 miR-130a-3p 升高对 SH-SY5Y 和 N2a 细胞凋亡以及 I/R 脑损伤的抑制作用。此外，H19 被证实与 SH-SY5Y 和 N2a 细胞中的 miR-130a-3p 结合。H19 和 miR-130a-3p 协同调节 SH-SY5Y 和 N2a 细胞凋亡以及 I/R 引起的脑损伤。总之，H19/miR-130a-3p/DAPK1 轴调节新生儿 HIE 的病理生理，提示新生儿 HIE 治疗的潜在治疗靶点。H19 被证实与 SH-SY5Y 和 N2a 细胞中的 miR-130a-3p 结合。H19 和 miR-130a-3p 协同调节 SH-SY5Y 和 N2a 细胞凋亡以及 I/R 引起的脑损伤。总之，H19/miR-130a-3p/DAPK1 轴调节新生儿 HIE 的病理生理，提示新生儿 HIE 治疗的潜在治疗靶点。H19 被证实与 SH-SY5Y 和 N2a 细胞中的 miR-130a-3p 结合。H19 和 miR-130a-3p 协同调节 SH-SY5Y 和 N2a 细胞凋亡以及 I/R 引起的脑损伤。总之，H19/miR-130a-3p/DAPK1 轴调节新生儿 HIE 的病理生理，提示新生儿 HIE 治疗的潜在治疗靶点。