Department of Histology and Embryology, School of Basic Medical Sciences, Southwest Medical University, Sichuan Province, China.
PLoS One. 2020 May 29;15(5):e0228825. doi: 10.1371/journal.pone.0228825. eCollection 2020.
Neonatal hypoxic-ischemic brain damage (HIBD) is prone to cognitive and memory impairments, and there is no effective clinical treatment until now. Ferulic acid (FA) is found within members of the genus Angelica, reportedly shows protective effects on neuronal damage. However, the protective effects of FA on HIBD remains unclear. In this study, using the Morris water maze task, we herein found that the impairment of spatial memory formation in adult rats exposed to HIBD was significantly reversed by FA treatment and the administration of LNA-miR-9. The expression of miRNA-9 was detected by RT-PCR analyses, and the results shown that miRNA-9 was significantly increased in the hippocampus of neonatal rats following HIBD and in the PC12 cells following hypoxic-ischemic injury, while FA and LNA-miR-9 both inhibited the expression of miRNA-9, suggesting that the therapeutic effect of FA was mainly attributed to the inhibition of miRNA-9 expression. Indeed, the silencing of miR-9 by LNA-miR-9 or FA similarly attenuated neuronal damage and cerebral atrophy in the rat hippocampus after HIBD, which was consistent with the restored expression levels of brain-derived neurotrophic factor (BDNF). Therefore, our findings indicate that FA treatment may protect against neuronal death through the inhibition of miRNA-9 induction in the rat hippocampus following hypoxic-ischemic damage.
新生儿缺氧缺血性脑损伤（HIBD）易发生认知和记忆障碍，目前尚无有效的临床治疗方法。阿魏酸（FA）存在于当归属植物中，据报道对神经元损伤具有保护作用。然而，FA 对 HIBD 的保护作用尚不清楚。在这项研究中，我们使用 Morris 水迷宫任务发现，FA 处理和 LNA-miR-9 给药可显著逆转 HIBD 成年大鼠空间记忆形成受损。通过 RT-PCR 分析检测 miRNA-9 的表达，结果表明，HIBD 后新生大鼠海马和缺氧缺血损伤后 PC12 细胞中 miRNA-9 的表达显著增加，而 FA 和 LNA-miR-9 均抑制 miRNA-9 的表达，表明 FA 的治疗作用主要归因于抑制 miRNA-9 的表达。事实上，通过 LNA-miR-9 或 FA 沉默 miR-9 同样减轻了 HIBD 后大鼠海马中的神经元损伤和脑萎缩，这与脑源性神经营养因子（BDNF）的表达水平恢复一致。因此，我们的研究结果表明，FA 治疗可能通过抑制缺氧缺血损伤后大鼠海马中 miRNA-9 的诱导来保护神经元死亡。
