Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
PLoS One. 2023 Jun 2;18(6):e0286686. doi: 10.1371/journal.pone.0286686. eCollection 2023.
Chronic intermittent hypoxia (CIH) induces oxidative stress in the brain, causing sleep disorders. Herein, we investigated the role of pterostilbene (Pte) in CIH-mediated oxidative stress in the brain tissue. A CIH mouse model was constructed by alternately reducing and increasing oxygen concentration in a sealed box containing the mouse; brain tissue and serum were then collected after intragastric administration of Pte. Neurological function was evaluated through field experiments. The trajectory of the CIH mice to the central region initially decreased and then increased after Pte intervention. Pte increased the number of neuronal Nissl bodies in the hippocampus of CIH mice, upregulated the protein levels of Bcl-2, occludin, and ZO-1 as well as the mRNA and protein levels of cAMP-response element binding protein (CREB) and p-BDNF, and reduced the number of neuronal apoptotic cells, Bax protein levels, IBA-1, and GFAP levels. Simultaneously, Pte reversed the decreased levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and BDNF and increased levels of malondialdehyde (MDA) in the serum of CIH mice. Pte increased Th2 cells, Treg cells, IL-4, IL-10, and TGF-β1 levels and decreased Th1 cells, Th17 cells, IFN-γ, IL-6, and IL- 17A levels in activated BV2 cells and hippocampus in CIH mice. The protein levels of p-ERK1/2, TLR4, p-p38, p-p65, and Bax, apoptosis rate, MDA concentration, Bcl-2 protein level, cell viability, and SOD and GSH-PX concentrations decreased after the activation of BV2 cells. Pte inhibited gliocytes from activating T-cell immune imbalance through p-ERK signaling to alleviate oxidative stress injury in nerve cells.
慢性间歇性低氧（CIH）会导致大脑氧化应激，引起睡眠障碍。本研究旨在探讨紫檀芪（Pte）在 CIH 介导的脑组织氧化应激中的作用。通过在密封箱中交替降低和增加含小鼠的氧气浓度来构建 CIH 小鼠模型，然后通过灌胃给予 Pte 来收集脑组织和血清。通过现场实验评估神经功能。CIH 小鼠向中央区域的轨迹在 Pte 干预后最初下降，然后增加。Pte 增加了 CIH 小鼠海马神经元尼氏小体的数量，上调了 Bcl-2、occludin 和 ZO-1 的蛋白水平以及 cAMP 反应元件结合蛋白（CREB）和 p-BDNF 的 mRNA 和蛋白水平，并减少了神经元凋亡细胞的数量，降低了 Bax 蛋白水平、IBA-1 和 GFAP 水平。同时，Pte 逆转了 CIH 小鼠血清中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）和 BDNF 水平的降低以及丙二醛（MDA）水平的升高。Pte 增加了 CIH 小鼠激活的 BV2 细胞和海马中的 Th2 细胞、Treg 细胞、IL-4、IL-10 和 TGF-β1 水平，并降低了 Th1 细胞、Th17 细胞、IFN-γ、IL-6 和 IL-17A 水平。BV2 细胞激活后，p-ERK1/2、TLR4、p-p38、p-p65 和 Bax 的蛋白水平、凋亡率、MDA 浓度、Bcl-2 蛋白水平、细胞活力以及 SOD 和 GSH-PX 浓度均降低。Pte 通过 p-ERK 信号抑制小胶质细胞激活 T 细胞免疫失衡，从而减轻神经细胞的氧化应激损伤。
