丁苯酞对氧糖剥夺后星形胶质细胞氧化损伤的保护作用研究

doi:10.3969/j.issn.1673-5765.2025.08.009

中国卒中杂志 ›› 2025, Vol. 20 ›› Issue (8): 1006-1012.DOI: 10.3969/j.issn.1673-5765.2025.08.009

丁苯酞对氧糖剥夺后星形胶质细胞氧化损伤的保护作用研究

高雨田，刘文娟，金玉玲，王克健

佳木斯 154002 佳木斯大学附属第一医院神经内科

收稿日期:2024-02-01 修回日期:2025-07-02 接受日期:2025-07-09 出版日期:2025-08-20 发布日期:2025-08-20
通讯作者: 金玉玲 342196990@qq.com
基金资助:
佳木斯大学新医科医学教育专项项目（2024XYK-34）

Protective Effects of 3-N-Butylphthalide against Oxygen-Glucose Deprivation-Induced Oxidative Damage in Astrocytes

GAO Yutian, LIU Wenjuan, JIN Yuling, WANG Kejian

Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, China

Received:2024-02-01 Revised:2025-07-02 Accepted:2025-07-09 Online:2025-08-20 Published:2025-08-20
Contact: JIN Yuling, E-mail: 342196990@qq.com

摘要/Abstract

摘要： 目的探讨丁苯酞（3-N-butylphthalide，NBP）对氧糖剥夺后星形胶质细胞氧化应激的保护作用及调节机制。
方法采用CTX TNA2大鼠星形胶质细胞构建氧糖剥夺模型，通过细胞计数试剂盒-8型评估细胞活性，检测超氧化物歧化酶（superoxide dismutase，SOD）活性与丙二醛（malondialdehyde，MDA）含量以评估氧化应激水平；使用实时荧光定量PCR检测细胞焦亡相关基因[胱天蛋白酶（cysteine aspartic acid specific protease，caspase）-1、核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3（nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3，NLRP3）、IL-1β、IL-18]的mRNA表达变化，并分析核转录因子红系2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf2）信号通路相关基因Nrf2及其下游基因血红素加氧酶（heme oxygenase，HO）-1的表达变化，以探讨其调控机制。
结果与对照组相比，氧糖剥夺组细胞活性（P=0.009）和SOD活性（P=0.013）显著降低，MDA含量显著升高（P=0.001）；caspase-1（P=0.018）、NLRP3（P=0.021）、IL-1β（P=0.004）及IL-18（P<0.001）mRNA水平显著升高，Nrf2（P=0.035）及HO-1（P=0.023）表达显著降低。与氧糖剥夺组相比，NBP组细胞活性（P=0.015）和SOD活性（P=0.013）显著升高，MDA含量（P=0.002）降低；同时，caspase-1（P=0.002）、NLRP3（P=0.009）、IL-1β（P=0.004）及IL-18（P=0.004）mRNA水平降低，Nrf2（P=0.027）及HO-1（P=0.001）基因表达升高。
结论 NBP可改善氧糖剥夺导致的星形胶质细胞氧化损伤，其可能通过激活Nrf2抗氧化通路、抑制焦亡信号，缓解氧糖剥夺诱导的氧化应激损伤，从而发挥潜在的细胞保护作用。

文章导读： 本研究发现NBP可能通过激活Nrf2/HO-1通路减轻氧糖剥夺后星形胶质细胞氧化应激损伤，同时抑制NLRP3/caspase-1介导的细胞焦亡，为开发星形胶质细胞靶向保护的卒中治疗策略提供了一定的依据。

关键词: 氧糖剥夺; 丁苯酞; 氧化应激; 焦亡; 核转录因子红系2相关因子2

Abstract: Objective To explore the protective effects and regulatory mechanisms of 3-N-butylphthalide (NBP) against oxidative stress in astrocytes subjected to oxygen-glucose deprivation.
Methods The oxygen-glucose deprivation model was established using CTX TNA2 rat astrocytes. Cell viability was assessed using the cell counting kit-8. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured to evaluate oxidative stress levels. Real time fluorogenic quantitative PCR was used to detect the changes in the mRNA expression of pyroptosis-related genes [cysteine aspartic acid specific protease (caspase)-1, nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), IL-1β, and IL-18]. Additionally, the expression changes of genes associated with the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway [Nrf2 and its downstream molecule heme oxygenase (HO)-1], were analyzed to explore their regulatory mechanisms.
Results Compared with the control group, the oxygen-glucose deprivation group exhibited significantly reduced cell viability (P=0.009) and SOD activity (P=0.013), alongside significantly elevated MDA content (P=0.001). The mRNA levels of caspase-1 (P=0.018), NLRP3 (P=0.021), IL-1β (P=0.004), and IL-18 (P<0.001) were significantly increased, whereas Nrf2 (P=0.035) and HO-1 (P=0.023) expression was significantly decreased. Compared with the oxygen-glucose deprivation group, the NBP-treated group demonstrated significantly increased cell viability (P=0.015) and SOD activity (P=0.013), with decreased MDA content (P=0.002). Concurrently, mRNA levels of caspase-1 (P=0.002), NLRP3 (P=0.009), IL-1β (P=0.004), and IL-18 (P=0.004) decreased, while Nrf2 (P=0.027) and HO-1 (P=0.001) expression increased.
Conclusions NBP can ameliorate oxygen-glucose deprivation-induced oxidative damage in astrocytes, potentially by activating the Nrf2 antioxidant pathway and inhibiting pyroptosis signaling, thereby alleviating oxygen-glucose deprivation-induced oxidative stress damage, and exerting a potential cytoprotective effects.

Key words: Oxygen-glucose deprivation; 3-N-butylphthalide; Oxidative stress; Pyroptosis; Nuclear factor erythroid 2-related factor 2

中图分类号:

高雨田, 刘文娟, 金玉玲, 王克健. 丁苯酞对氧糖剥夺后星形胶质细胞氧化损伤的保护作用研究[J]. 中国卒中杂志, 2025, 20(8): 1006-1012.

GAO Yutian, LIU Wenjuan, JIN Yuling, WANG Kejian. Protective Effects of 3-N-Butylphthalide against Oxygen-Glucose Deprivation-Induced Oxidative Damage in Astrocytes[J]. Chinese Journal of Stroke, 2025, 20(8): 1006-1012.

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丁苯酞对氧糖剥夺后星形胶质细胞氧化损伤的保护作用研究

Protective Effects of 3-N-Butylphthalide against Oxygen-Glucose Deprivation-Induced Oxidative Damage in Astrocytes

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