首页|反应氧族促进神经保护的量效关系及其机制研究

反应氧族促进神经保护的量效关系及其机制研究

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反应氧族(ROS)的大量产生是缺血性中风损伤的关键因素.尽管大量研究表明抗氧化剂具有神经保护作用,然而其长期临床疗效始终差强人意.事实上,ROS在特定浓度下具有促进细胞增殖、促进保护性自噬、激活自身抗氧化能力等积极的生理作用,在抗氧化干预时尽量保留ROS的优势作用或是解决问题的关键.本研究探索了不同剂量下H2O2对PC12和SH-SY5Y神经细胞增殖、自噬、凋亡等生理病理功能的影响,检测了相应细胞内及线粒体内ROS的变化规律,绘制了ROS发挥优势活性的剂量区间.进一步使用自噬抑制剂及信号通路抑制剂等进行研究,结果表明100 μM的H2O2可通过AKT/m-TOR介导的HIF-1α和TFEB信号激活保护性自噬,从而实现神经细胞的保护作用.本研究揭示了ROS发挥优势作用的浓度范围,并阐明了其神经保护机制,为全面优化脑缺血后抗氧化剂的使用提供了重要参考.
Study on the dose-effect relationship and mechanism of reactive oxygen species promoted neuroprotection
The overproduction of reactive oxygen species(ROS)is widely acknowledged as a pivotal factor in the occurrence of ischemic stroke injuries.While numerous experimental studies have demonstrated the significant neuroprotective effects of antioxidants,their long-term clinical efficacy has consistently fallen short of expectations.Interestingly,ROS can exert positive physiological effects,such as promoting cell proliferation,activating protective autophagy,and enhancing antioxidant capacity,at certain concentrations.Consequently,preserving the advantageous aspects of ROS is crucial for addressing the limitations of antioxidant therapy.This study investigated the impact of ROS at varying concentrations on physiological and pathological functions,including neural cell proliferation,autophagy,and apoptosis.We also assessed the fluctuations in intracellular and mitochondrial ROS levels and delineated the dose range within which these advantageous functions occur.Additionally,we conducted further research using autophagy inhibitors and signaling pathway inhibitors.The findings demonstrated that 100 μM H2O2 could induce protective autophagy through HIF-1α and TFEB signaling pathways mediated by AKT/m-TOR,thereby conferring a protective effect on nerve cells.This study elucidated the concentration range at which ROS exerted a protective role and unraveled its neuroprotective mechanism,offering a crucial reference for optimizing the comprehensive application of antioxidants following cerebral ischemia.

Reactive oxygen speciesCerebral ischemiaProtective autophagyHIF-1αTFEB

黄荣、胡小娇、张润芳、李晓晖、岑娟

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河南大学第一附属医院神经内科,河南开封 475000

河南大学药学院天然药物与免疫工程重点实验室,河南开封 475004

反应氧族 脑缺血 保护性自噬 HIF-1α TFEB

Henan Medical Science and Technology Research Program(Joint Construction Project)Funded ProjectProject of Kaifeng Science and Technology Bureau

20180203172003033

2024

10.5246/jcps.2024.01.005

中国药学(英文版)
中国药学会

中国药学(英文版)

CSTPCD
影响因子：0.534
ISSN：1003-1057
年,卷(期)：2024.33(1)
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