Department of Anesthesiology, Second Affiliated Hospital of Naval Medical University, No. 415, Fengyang Road, Huangpu District, 200003, Shanghai, China.
Neurochem Res. 2021 Dec;46(12):3356-3364. doi: 10.1007/s11064-021-03436-5. Epub 2021 Sep 15.
Sevoflurane is a widely used volatile anesthetic, that can cause long-term neurotoxicity and learning and memory impairment. Long non-coding RNAs (lncRNAs) have been demonstrated to function as key mediators in neurotoxicity. This study aimed to investigate the effects of lncRNA Neat1 on sevoflurane-induced neurotoxicity. The expression of Neat1, miR-298-5p, and Srpk1 was measured by RT-qPCR. Cell viability, cell apoptosis, inflammation markers, and reactive oxygen species (ROS) generation were examined by CCK-8, TUNEL, ELISA, and the ROS kit. The interaction between miR-298-5p and Neat1 or Srpk1 was confirmed by luciferase reporter assay. In our study, it was found that sevoflurane aggravated neurotoxicity through inhibiting cell viability and enhancing cell apoptosis, neuroinflammation, and ROS generation. Neat1 was up-regulated in sevoflurane-treated HT22 cells, and Neat1 knockdown improved sevoflurane-mediated neurotoxicity. Through the exploration of the ceRNA mechanism, we found that Neat1 bound with miR-298-5p, and Srpk1 was a direct target gene of miR-298-5p. Finally, rescue assays proved that up-regulation of Srpk1 reversed the effects of Neat1 knockdown on neurotoxicity. In conclusion, our study revealed that lncRNA Neat1 facilitated sevoflurane-stimulated neurotoxicity by sponging miR-298-5p to up-regulate Srpk1. These findings might provide novel insights into the treatment of sevoflurane-induced neurotoxicity.
七氟醚是一种广泛应用的挥发性麻醉剂，可导致长期的神经毒性和学习记忆障碍。长链非编码 RNA（lncRNA）已被证明在神经毒性中作为关键介质发挥作用。本研究旨在探讨 lncRNA Neat1 对七氟醚诱导的神经毒性的影响。通过 RT-qPCR 测量 Neat1、miR-298-5p 和 Srpk1 的表达。通过 CCK-8、TUNEL、ELISA 和 ROS 试剂盒检测细胞活力、细胞凋亡、炎症标志物和活性氧（ROS）生成。通过荧光素酶报告基因测定证实了 miR-298-5p 与 Neat1 或 Srpk1 之间的相互作用。在我们的研究中，发现七氟醚通过抑制细胞活力和增强细胞凋亡、神经炎症和 ROS 生成来加重神经毒性。Neat1 在七氟醚处理的 HT22 细胞中上调，Neat1 敲低改善了七氟醚介导的神经毒性。通过 ceRNA 机制的探索，我们发现 Neat1 与 miR-298-5p 结合，Srpk1 是 miR-298-5p 的直接靶基因。最后，挽救实验证明上调 Srpk1 逆转了 Neat1 敲低对神经毒性的影响。总之，本研究表明 lncRNA Neat1 通过海绵 miR-298-5p 上调 Srpk1 促进七氟醚刺激的神经毒性。这些发现可能为七氟醚诱导的神经毒性的治疗提供新的思路。
