Department of Physical Examination, Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, 200040, China.
Department of Anesthesiology, Jing'an District Centre Hospital of Shanghai, Fudan University, No. 259 Xikang Road, Shanghai, 200040, China.
J Mol Neurosci. 2024 Oct 16;74(4):97. doi: 10.1007/s12031-024-02277-5.
Sevoflurane causes neural injury by promoting apoptosis and oxidative stress. Reactive oxygen species modulator 1 (ROMO1) regulates apoptosis and oxidative stress, while its role in sevoflurane-induced neural injury remains unclear. This study intended to investigate the effect of ROMO1 knockdown on viability, apoptosis, and oxidative stress in sevoflurane-treated HT22 cells and its downstream pathway. HT22 cells were untreated (blank control), or treated with 1%, 2%, and 4% sevoflurane, respectively. Moreover, HT22 cells were transfected with siROMO1 small interfering RNA (siROMO1) or negative control siRNA (siNC) and then stimulated with 4% sevoflurane for further assays. Sevoflurane dose-dependently decreased cell viability and increased apoptosis rate versus blank control in HT22 cells. Sevoflurane elevated reactive oxygen species (ROS) fluorescence intensity, malondialdehyde (MDA), and lactate dehydrogenase (LDH) release, while reducing superoxide dismutase (SOD) activity in a dose-dependent manner versus blank control in HT22 cells. It also dose-dependently increased the relative mRNA and protein expressions of ROMO1 versus blank treatment in HT22 cells. Moreover, siROMO1 plus 4% sevoflurane increased cell viability, while decreasing apoptosis rate, ROS fluorescence intensity, MDA, and LDH release versus siNC plus 4% sevoflurane in HT22 cells. siROMO1 plus 4% sevoflurane elevated the phosphorylation of protein kinase B (AKT) versus siNC plus 4% sevoflurane in HT22 cells. ROMO1 inhibition reverses sevoflurane-induced neural injury by reducing apoptosis and oxidative stress in HT22 cells. The results indicate that ROMO1 may be a potential target for the management of sevoflurane-induced neural injury.
七氟醚通过促进细胞凋亡和氧化应激引起神经损伤。活性氧调节剂 1（ROMO1）调节细胞凋亡和氧化应激，但其在七氟醚诱导的神经损伤中的作用尚不清楚。本研究旨在探讨 ROMO1 敲低对七氟醚处理的 HT22 细胞活力、凋亡和氧化应激的影响及其下游通路。HT22 细胞未经处理（空白对照），或分别用 1%、2%和 4%七氟醚处理，此外，HT22 细胞用 siROMO1 小干扰 RNA（siROMO1）或阴性对照 siRNA（siNC）转染，然后用 4%七氟醚进一步刺激进行检测。与空白对照相比，七氟醚呈剂量依赖性降低 HT22 细胞活力，增加细胞凋亡率。七氟醚呈剂量依赖性增加 HT22 细胞活性氧（ROS）荧光强度、丙二醛（MDA）和乳酸脱氢酶（LDH）释放，同时降低超氧化物歧化酶（SOD）活性，与空白对照相比。与空白处理相比，HT22 细胞中 ROMO1 的相对 mRNA 和蛋白表达也呈剂量依赖性增加。此外，与 siNC 加 4%七氟醚相比，siROMO1 加 4%七氟醚增加了 HT22 细胞活力，降低了细胞凋亡率、ROS 荧光强度、MDA 和 LDH 释放。与 siNC 加 4%七氟醚相比，siROMO1 加 4%七氟醚使 HT22 细胞中蛋白激酶 B（AKT）磷酸化升高。ROMO1 抑制通过减少 HT22 细胞中的细胞凋亡和氧化应激逆转七氟醚引起的神经损伤。结果表明，ROMO1 可能是管理七氟醚诱导的神经损伤的潜在靶点。
