右美托咪定通过激活PINK1/Parkin通路激活氧葡萄糖剥夺/再灌注诱导的脑损伤,激活线粒体自噬并防止焦亡。

IF 2.9 4区 生物学 Q2 BIOPHYSICS
Jieru Zhang, Ruxia Li, Luyong Wang, Shuqin Ni
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引用次数: 0

摘要

越来越多的研究表明,右美托咪定(DEX)对大脑损伤具有神经保护作用。然而,DEX的神经保护作用的机制仍然是未知的。因此,本研究探讨DEX是否会影响缺氧缺血性脑损伤的线粒体自噬和焦亡。建立氧葡萄糖剥夺(OGD)海马神经元模型和脑缺血再灌注(I/R)损伤大鼠模型,给予DEX和自噬抑制剂(3-MA)干预。结果发现,DEX干预可显著增加神经元活力和线粒体自噬。此外,DEX干预逆转了OGD引起的氧化应激和焦亡的增加。DEX干预进一步维持了PINK1/Parkin通路的激活,而3-MA处理部分抵消了DEX对ogd诱导的海马神经元的保护作用,提示PINK1/Parkin通路的抑制逆转了DEX提高细胞活力和线粒体自噬、抑制氧化应激、焦亡和凋亡的功能。动物实验还发现,DEX干预可诱导PINK1/Parkin通路激活,减少脑梗死和线粒体损伤,促进线粒体自噬,抑制焦亡,3-MA处理可消除这一作用。总之,DEX通过激活PINK1/Parkin通路,在OGD/ r诱导的脑损伤中保护焦亡并激活有丝分裂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dexmedetomidine activates mitophagy and protects against pyroptosis in oxygen-glucose deprivation/reperfusion-induced brain damage via PINK1/Parkin pathway activation.

Accumulating studies have unraveled that dexmedetomidine (DEX) is neuroprotective against brain damage. However, it remains largely unknown about the mechanism involved in the neuroprotective effect of DEX. Therefore, this study explored whether DEX could affect mitophagy and pyroptosis in hypoxic-ischemic brain damage. We established a hippocampal neuron model of oxygen glucose-deprivation (OGD) and a rat model of cerebral ischemia/reperfusion (I/R) injury, which were then intervened with DEX and the autophagy inhibitor (3-MA). It was found that DEX intervention significantly increased neuron viability and mitophagy. Additionally, DEX intervention reversed increased oxidative stress and pyroptosis caused by OGD. DEX intervention further maintained the activation of the PINK1/Parkin pathway, while 3-MA treatment partly counteracted the protective effect of DEX on OGD-induced hippocampal neurons, suggesting that the inhibition of the PINK1/Parkin pathway reversed the function of DEX to increase cell viability and mitophagy and inhibit oxidative stress, pyroptosis, and apoptosis. Animal experiments also revealed that DEX intervention induced PINK1/Parkin pathway activation, reduced cerebral infarction and mitochondrial damage, promoted mitophagy, and inhibited pyroptosis, which was nullified by 3-MA treatment. Conclusively, DEX protects against pyroptosis and activates mitophagy in OGD/R-induced brain damage by activating the PINK1/Parkin pathway.

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来源期刊
CiteScore
6.00
自引率
0.00%
发文量
22
审稿时长
6-12 weeks
期刊介绍: The Journal of Bioenergetics and Biomembranes is an international journal devoted to the publication of original research that contributes to fundamental knowledge in the areas of bioenergetics, biomembranes, and transport, including oxidative phosphorylation, photosynthesis, muscle contraction, as well as cellular and systemic metabolism. The timely research in this international journal benefits biophysicists, membrane biologists, cell biologists, biochemists, molecular biologists, physiologists, endocrinologists, and bio-organic chemists.
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