Subarachnoid hemorrhage (SAH) is a neurological disorder that severely damages the brain and causes cognitive impairment. MicroRNAs are critical regulators in a variety of neurological diseases. MiR-497-5p has been found to be downregulated in the aneurysm vessel walls obtained from patients with aneurysmal subarachnoid hemorrhage, but its functions and mechanisms in SAH have not been reported. Therefore, this study was designed to investigate the effect of miR-497-5p and its related mechanisms in SAH. We established an in vitro SAH model by exposing PC12 cells to oxyhemoglobin (oxyHb). We found that miR-497-5p was downregulated in SAH serum and oxyHb-treated PC12 cells, and its overexpression inhibited the oxyHb-induced apoptosis, inflammatory response and oxidative stress via activation of the Nrf2 pathway. Mechanistically, the targeting relationship between miR-497-5p and Otx1 was verified by luciferase reporter assays. Moreover, Otx1 upregulation abolished the protective effects of miR-497-5p upregulation against oxyHb-induced apoptosis, inflammation and oxidative stress in PC12 cells. Collectively, our findings indicate that miR-497-5p could inhibit the oxyHb-induced SAH damage by targeting Otx1 to activate the Nrf2/HO-1 pathway, which provides a potential therapeutic target for SAH treatment.

蛛网膜下腔出血（SAH）是一种神经系统疾病，会严重损害大脑并导致认知障碍。 MicroRNA 是多种神经系统疾病的关键调节因子。已发现 MiR-497-5p 在动脉瘤性蛛网膜下腔出血患者的动脉瘤血管壁中表达下调，但其在 SAH 中的功能和机制尚未见报道。因此，本研究旨在探讨miR-497-5p在SAH中的作用及其相关机制。我们通过将 PC12 细胞暴露于氧合血红蛋白 (oxyHb) 建立了体外 SAH 模型。我们发现 miR-497-5p 在 SAH 血清和 oxyHb 处理的 PC12 细胞中下调，其过表达通过激活 Nrf2 通路抑制 oxyHb 诱导的细胞凋亡、炎症反应和氧化应激。从机制上讲，miR-497-5p 和 Otx1 之间的靶向关系通过荧光素酶报告基因测定得到验证。此外，Otx1 上调消除了 miR-497-5p 上调对 oxyHb 诱导的 PC12 细胞凋亡、炎症和氧化应激的保护作用。总的来说，我们的研究结果表明，miR-497-5p可以通过靶向Otx1激活Nrf2/HO-1通路来抑制oxyHb诱导的SAH损伤，这为SAH治疗提供了潜在的治疗靶点。