3-n-butyphthal de exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke
3-n-butyphthal de exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke
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DOI：
10.2147/dddt.s189472
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发表时间：
2018-01-01
影响因子：
4.8
通讯作者：
Zhang, Jianfeng
中科院分区：
文献类型：
--
作者：
Chen, Ningyuan;Zhou, Zhibing;Zhang, Jianfeng
目的：本研究探讨用于治疗缺血性中风的神经保护药物3-正丁基苯酞（NBP）是否可以预防线粒体功能障碍。 材料与方法：PC12神经元细胞用NBP（10 μmol/L）预处理24小时，然后暴露于氧糖剥夺（OGD）8小时作为实验条件。 缺血性中风的体外模型。评估抗氧化反应、线粒体功能和线粒体动力学指标。结果：OGD 抑制细胞活力，诱导细胞凋亡并增加 caspase-3 活性。 NBP 显着扭转了这些影响。 NBP 通过增加超氧化物歧化酶的活性并降低丙二醛 (M DA) 和活性氧 (ROS) 的水平来防止氧化损伤。同时，它增加了Nrf2、HO-1和AMPK的表达。 N BP 通过增强线粒体膜电位和增加线粒体呼吸链复合物 I-IV 和 ATP 酶的活性来减轻线粒体功能障碍。 NBP 改变了调节线粒体融合和分裂的蛋白质的平衡。结论：NBP 通过增强抗氧化和减轻线粒体功能障碍而发挥神经保护作用。我们的研究结果深入了解了 NBP 如何在缺血性中风中发挥神经保护作用，并提出了它可能对涉及线粒体功能障碍的其他神经退行性疾病具有类似作用的可能性。
Purpose: This study examined whether the neuroprotective drug, 3-n-butylphthalide (NBP), which is used to treat ischemic stroke, prevents mitochondrial dysfunction.Materials and methods: PC12 neuronal cells were pretreated for 24 hours with NBP (10 mu mol/L), then exposed to oxygen and glucose deprivation (OGD) for 8 hours as an in vitro model of ischemic stroke. Indices of anti-oxidative response, mitochondrial function and mitochondrial dynamics were evaluated.Results: OGD suppressed cell viability, induced apoptosis and increased caspase-3 activity. NBP significantly reversed these effects. NBP prevented oxidative damage by increasing the activity of superoxide dismutase and lowering levels of malondialdehyde (M DA) and reactive oxygen species (ROS). At the same time, it increased expression of Nrf2, HO-1 and AMPK. N BP attenuated mitochondrial dysfunction by enhancing mitochondrial membrane potential and increasing the activity of mitochondrial respiratory chain complexes I-IV and ATPase. NBP altered the balance of proteins regulating mitochondrial fusion and division.Conclusion: NBP exerts neuroprotective actions by enhancing anti-oxidation and attenuating mitochondrial dysfunction. Our findings provide insight into how NBP may exert neuroprotective effects in ischemic stroke and raise the possibility that it may function similarly against other neurodegenerative diseases involving mitochondrial dysfunction.