Department of Anesthesiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China (mainland).
Department of Radiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China (mainland).
Med Sci Monit. 2021 Jun 1;27:e930042. doi: 10.12659/MSM.930042.
BACKGROUND Perinatal hypoxia and subsequent reduction of cerebral blood flow leads to neonatal hypoxic-ischemic brain injury (HIBI), resulting in severe disability and even death. Preconditioning or post-conditioning with sevoflurane protects against cerebral injury. This study investigated the mechanism of sevoflurane in HIBI. MATERIAL AND METHODS The HIBI model of neonatal rats was established and the model rats were post-treated with sevoflurane. The oxygen-glucose deprivation (OGD) cell model was established, and the OGD cells were transfected with NRF2-siRNA plasmid and post-treated with sevoflurane. The Morris water maze test was used to detect the motor activity, spatial learning, and memory ability of HIBI rats. Histological stainings were performed to observe the area of cerebral infarction, record the number of neurons in the hippocampus, and assess neuron apoptosis. The levels of inflammatory factors were detected by ELISA. The protein levels of histone methyltransferase G9a and histone H3 lysine 9 (H3K9me2) were detected by western blot assay. The apoptosis was detected by flow cytometry. RESULTS Sevoflurane post-treatment significantly shortened the escape latency of HIBI neonatal rats, increased the density of neurons, reduced the area of cerebral infarction, and decreased the levels of inflammatory factors and neuronal apoptosis. Sevoflurane post-treatment decreased G9a and H3K9me2 levels, and G9a level was negatively correlated with NRF2 level. NRF2 silencing reversed the alleviation of sevoflurane post-treatment on OGD-induced cell injury. CONCLUSIONS Sevoflurane post-treatment promotes NRF2 expression by inhibiting G9a and H3K9me2, thus alleviating HIBI in neonatal rats.
围产期缺氧及随后脑血流减少可导致新生儿缺氧缺血性脑损伤（HIBI），导致严重残疾甚至死亡。七氟醚预处理或后处理可保护脑损伤。本研究探讨了七氟醚在 HIBI 中的作用机制。
建立新生大鼠 HIBI 模型，对模型大鼠进行七氟醚后处理。建立氧葡萄糖剥夺（OGD）细胞模型，用 NRF2-siRNA 质粒转染 OGD 细胞，并用七氟醚后处理。采用 Morris 水迷宫实验检测 HIBI 大鼠的运动活动、空间学习和记忆能力。进行组织学染色观察脑梗死面积，记录海马神经元数量，评估神经元凋亡。通过 ELISA 检测炎症因子水平。通过 Western blot 检测组蛋白甲基转移酶 G9a 和组蛋白 H3 赖氨酸 9（H3K9me2）的蛋白水平。通过流式细胞术检测细胞凋亡。
七氟醚后处理显著缩短了 HIBI 新生大鼠的逃避潜伏期，增加了神经元密度，减少了脑梗死面积，降低了炎症因子和神经元凋亡水平。七氟醚后处理降低了 G9a 和 H3K9me2 水平，G9a 水平与 NRF2 水平呈负相关。NRF2 沉默逆转了七氟醚后处理对 OGD 诱导的细胞损伤的缓解作用。
七氟醚后处理通过抑制 G9a 和 H3K9me2 促进 NRF2 表达，从而减轻新生大鼠的 HIBI。
Zotero 插件
