Qian Jing, Dai Xiaoxiao, Li Zhaoxuan
Department of Anesthesiology, Yancheng Third People's Hospital, Yancheng City, Jiangsu Province, China.
Department of Anesthesiology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng City, Jiangsu Province, China.
Neurochem Res. 2025 Sep 11;50(5):295. doi: 10.1007/s11064-025-04537-1.
To investigate the role and mechanism of long non-coding RNA PVT1 in sevoflurane-induced oxidative stress and cognitive dysfunction. The expression level of PVT1 and the mRNA expressions of Caspase-3, Bax, and Bcl2 were detected by RT-qPCR. Cell viability and apoptosis rate were evaluated by MTT assay and flow cytometry, respectively. The levels of malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD) were determined using commercial kits. The cognitive function of rats was assessed by Morris water maze (MWM) test. Online databases were used to predict the microRNAs (miRNAs) targeted by PVT1, and dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the targeted binding relationship. PVT1 levels were significantly upregulated in hippocampal tissues of rats and HT22 cells treated with sevoflurane. Silencing of PVT1 effectively alleviated sevoflurane-induced cell apoptosis, oxidative stress, and cognitive dysfunction. Mechanistic studies showed that PVT1 targeted miR-486-5p. In sevoflurane-treated hippocampal tissues of rats and HT22 cells, inhibition of miR-486-5p counteracted the protective effects of PVT1 silencing, leading to increased cell apoptosis, exacerbated oxidative stress, and deteriorated cognitive dysfunction. PVT1 silencing mitigates oxidative stress response and cognitive dysfunction by targeting miR-486-5p, providing a novel research perspective for the treatment of sevoflurane-induced nerve injury.
探讨长链非编码RNA PVT1在七氟醚诱导的氧化应激和认知功能障碍中的作用及机制。通过RT-qPCR检测PVT1的表达水平以及Caspase-3、Bax和Bcl2的mRNA表达。分别采用MTT法和流式细胞术评估细胞活力和凋亡率。使用商业试剂盒测定丙二醛（MDA）、活性氧（ROS）和超氧化物歧化酶（SOD）的水平。通过莫里斯水迷宫（MWM）试验评估大鼠的认知功能。利用在线数据库预测PVT1靶向的微小RNA（miRNA），并进行双荧光素酶报告基因检测和RNA免疫沉淀（RIP）试验以验证靶向结合关系。在七氟醚处理的大鼠海马组织和HT22细胞中，PVT1水平显著上调。沉默PVT1可有效减轻七氟醚诱导的细胞凋亡、氧化应激和认知功能障碍。机制研究表明，PVT1靶向miR-486-5p。在七氟醚处理的大鼠海马组织和HT22细胞中，抑制miR-486-5p可抵消PVT1沉默的保护作用，导致细胞凋亡增加、氧化应激加剧和认知功能障碍恶化。PVT1沉默通过靶向miR-486-5p减轻氧化应激反应和认知功能障碍，为七氟醚诱导的神经损伤治疗提供了新的研究视角。
