Abstract Hypoxic-ischaemic encephalopathy (HIE) resulting from perinatal asphyxia or intrapartum-related events is a common cause of neonatal brain damage death among neonatal brain injury and term infants. However, the potential mechanisms of brain injury in term infants with HIE remain to be elucidated. This study aimed to investigate the role of miR-454-3p in HIE. The protective effect of microRNA-454-3p (miR-454-3p) targeting ST18 on neonatal HIE was investigated by the HIE rat model and primary rat nerve cell oxygen and glucose deprivation (OGD) model. The expression of miR-454-3p was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell apoptosis and viability was detected by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, respectively. TargetScan predicted the binding sites between miR-454-3p and ST18. Dual luciferase reporter system was used to validate the relationship between ST18 and miR-454-3p. We found a significant decrease in miR-454-3p expression in the brain tissue of rats with HIE, while apoptosis and S100B and neuron-specific enolase (NSE) expression were significantly increased. In addition, miR-454-3p was significantly decreased in OGD-induced neurons, while the mRNA and protein expression of ST18 was significantly increased. OGD reduced neuronal cell viability and increased cell apoptosis were significantly inhibited by miR-454-3p mimic, but all these effects were significantly reversed by over-expression of ST18 gene. In conclusion, our study suggested that miR-454-3p was down-regulated in HIE rats, and it could attenuate OGD-induced neuronal apoptosis by targeting ST18, thereby playing a protective role in HIE, which might become a new and effective therapeutic target for HIE.

中文翻译：

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microRNA-454-3p通过靶向ST18对新生儿缺氧缺血性脑病的保护作用

摘要 围产期窒息或产时相关事件导致的缺氧缺血性脑病 (HIE) 是新生儿脑损伤和足月儿新生儿脑损伤死亡的常见原因。然而，HIE足月儿脑损伤的潜在机制仍有待阐明。本研究旨在探讨 miR-454-3p 在 HIE 中的作用。通过HIE大鼠模型和原代大鼠神经细胞氧和葡萄糖剥夺（OGD）模型研究靶向ST18的microRNA-454-3p（miR-454-3p）对新生儿HIE的保护作用。通过定量逆转录聚合酶链反应 (qRT-PCR) 检测 miR-454-3p 的表达。分别通过流式细胞术和3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-溴化四唑(MTT)测定法检测细胞凋亡和活力。TargetScan 预测了 miR-454-3p 和 ST18 之间的结合位点。双荧光素酶报告系统用于验证 ST18 和 miR-454-3p 之间的关系。我们发现 HIE 大鼠脑组织中 miR-454-3p 表达显着降低，而细胞凋亡和 S100B 和神经元特异性烯醇化酶 (NSE) 表达显着增加。此外，OGD 诱导的神经元中 miR-454-3p 显着降低，而 ST18 的 mRNA 和蛋白质表达显着增加。miR-454-3p 模拟物显着抑制 OGD 降低神经元细胞活力和增加细胞凋亡，但所有这些影响都被 ST18 基因的过度表达显着逆转。总之，我们的研究表明 miR-454-3p 在 HIE 大鼠中下调，