Li Xiuli, Li Xuefei, Liang Yinan
Department of Anesthesiology, Pengzhou People's Hospital , No. 255 South Third Ring Road, Pengzhou 611930, China.
Department of Anesthesiology, The Second People's Hospital of Pidu District of Chengdu, No. 86 Southeast Section of the Second Ring Road, Pidu District, Chengdu 611733, China.
Toxicol Res (Camb). 2024 Aug 19;13(4):tfae132. doi: 10.1093/toxres/tfae132. eCollection 2024 Aug.
Sevoflurane (Sev), a widely used volatile anesthetic, can cause neurotoxicity, and impair learning and memory.
This study investigates the role and mechanisms of circHIPK3 in Sev-exposed neurotoxicity and learning and memory impairment.
SD rats and hippocampal neuronal cells were exposed to Sev. RT-qPCR analysis of circHIPK3 and miR-338-3p levels. MWM test was performed to examine the behavioral changes in rats. The levels of circHIPK3 and miR-338-3p levels were investigated using RT-qPCR. ELISA assay to analyze the expression of pro-inflammatory factors. CCK-8, flow cytometry, and commercial ROS assay kits were analyzed to detect cell viability, apoptosis, and ROS production. DLR and RIP assays validate circHIPK3 binding to miR-338-3p.
Sev increased circHIPK3 expression in rat hippocampal tissue as well as in neuronal cells but decreased miR-338-3p levels compared to controls. circHIPK3 binding to miR-338-3p. Furthermore, silencing of circHIPK3 rats attenuated Sev-induced decline in learning and memory functions . silencing circHIPK3 also reduced Sev-induced secretion of inflammatory factors in rat and neuronal cells. Reducing circHIPK3 partially reversed the Sev-induced decrease in cell viability, increased apoptosis, and overproduction of ROS. However, the inhibitory effect of circHIPK3 on Sev neurotoxicity was restored upon downregulation of miR-338-3p.
Collectively, silencing circHIPK3 alleviates Sev exposure-induced learning and memory deficits and neurotoxicity by enhancing miR-338-3p expression.
七氟醚（Sev）是一种广泛使用的挥发性麻醉剂，可导致神经毒性，并损害学习和记忆。
本研究探讨环状HIPK3（circHIPK3）在七氟醚暴露所致神经毒性及学习记忆损害中的作用及机制。
将SD大鼠和海马神经元细胞暴露于七氟醚。采用RT-qPCR分析circHIPK3和miR-338-3p水平。进行 Morris水迷宫（MWM）试验以检测大鼠的行为变化。采用RT-qPCR研究circHIPK3和 miR-338-3p水平。采用酶联免疫吸附测定（ELISA）分析促炎因子的表达。采用细胞计数试剂盒（CCK-8）、流式细胞术和商业活性氧（ROS）检测试剂盒分析检测细胞活力、凋亡和ROS产生。采用双荧光素酶报告基因（DLR）和RNA免疫沉淀（RIP）试验验证circHIPK3与miR-338-3p的结合。
与对照组相比，七氟醚增加了大鼠海马组织及神经元细胞中circHIPK3的表达，但降低了miR-338-3p水平。circHIPK3与miR-338-3p结合。此外，沉默circHIPK3可减轻七氟醚诱导的大鼠学习记忆功能下降。沉默circHIPK3还可减少七氟醚诱导大鼠及神经元细胞炎性因子的分泌。降低circHIPK3可部分逆转七氟醚诱导的细胞活力下降、凋亡增加和ROS过量产生。然而，下调miR-338-3p后，circHIPK3对七氟醚神经毒性的抑制作用得以恢复。
总体而言，沉默circHIPK3可通过增强miR-338-3p表达减轻七氟醚暴露诱导的学习记忆缺陷和神经毒性。
