Department of Neurology, Taizhou First People's Hospital, Taizhou, Zhejiang, China.
Neuroreport. 2021 Dec 8;32(17):1370-1378. doi: 10.1097/WNR.0000000000001738.
Ketamine is clinically used as a narcotic. However, ketamine has certain deficits and produces toxicity to neurons. As a member of the NR4A receptor subfamily, Nur77 decreases neurodegenerative disorders. The study aims to investigate the effects of upregulated Nur77 on ketamine-induced rat hippocampal neurons damage and the active mechanism. Neurons were obtained from rat hippocampal and identified by immunofluorescence assays. The treatment groups contained ketamine group, Nur77 group, ketamine + Nur77 group and ketamine + L-cam group. Neurons apoptosis and reactive oxygen species (ROS) were determined by a related kit using flow cytometry. Enzyme NAD(P)H quinone oxidoreductase 1 (NQO1), enzyme heme oxygenase 1 (HO1), Nur77, the expression of Bax, Bcl-2 and cleaved-caspase-3 and inflammatory cytokines were measured using western blot assays and reverse transcription-quantitative PCR (RT-qPCR) assays. Ketamine-induced neurons apoptosis; however, Nur77 decreased ketamine-induced neurons apoptosis. A low level of ROS was observed in two combination groups. Neurons treated by ketamine only had the lowest levels of Nur77, NQO1 and HO1, compared with other treatment groups. The levels of Bax and cleaved-caspase-3 in two combination groups were lower than those in the ketamine group. Furthermore, the ketamine group had higher levels of tumor necrosis factor alpha, IL-1β and IL-6 but the lowest level of IL-4. Upregulated Nur77 reduced the ketamine-induced toxicity in neurons. The mechanism of Nur77 involved antioxidation, apoptosis signaling pathway and inflammation signaling pathway. Our study provides a novel therapy that could attenuate ketamine-induced toxicity.
氯胺酮在临床上被用作麻醉剂。然而，氯胺酮有一定的缺陷，会对神经元产生毒性。Nur77 作为 NR4A 受体亚家族的一员，可减少神经退行性疾病。本研究旨在探讨上调 Nur77 对氯胺酮诱导的大鼠海马神经元损伤的作用及其作用机制。神经元取自大鼠海马并通过免疫荧光法鉴定。处理组包括氯胺酮组、Nur77 组、氯胺酮+Nur77 组和氯胺酮+L-cam 组。通过流式细胞术利用相关试剂盒测定神经元凋亡和活性氧（ROS）。采用 Western blot 和逆转录-定量 PCR（RT-qPCR）测定酶 NAD(P)H 醌氧化还原酶 1（NQO1）、酶血红素加氧酶 1（HO1）、Nur77、Bax、Bcl-2 和 cleaved-caspase-3 的表达以及炎症细胞因子。氯胺酮诱导神经元凋亡；然而，Nur77 降低了氯胺酮诱导的神经元凋亡。两个联合组的 ROS 水平较低。与其他处理组相比，仅用氯胺酮处理的神经元 Nur77、NQO1 和 HO1 水平最低。两个联合组的 Bax 和 cleaved-caspase-3 水平低于氯胺酮组。此外，氯胺酮组肿瘤坏死因子-α、IL-1β 和 IL-6 水平较高，但 IL-4 水平最低。上调 Nur77 减轻了氯胺酮诱导的神经元毒性。Nur77 的作用机制涉及抗氧化、凋亡信号通路和炎症信号通路。本研究为减轻氯胺酮诱导的毒性提供了一种新的治疗方法。
