The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1‐mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia‐reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR‐treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1‐related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR‐treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti‐apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK‐Mfn1 pathway.

中文翻译：

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白藜芦醇通过调节线粒体动态稳态并激活AMPK-Mfn1通路来减轻脑缺血再灌注损伤。

脑缺血再灌注损伤（IRI）的发病机理尚未完全描述。因此，几乎没有有效的药物可用于治疗脑IRI。我们研究的目的是探讨Mfn1介导的线粒体保护在脑IRI中的确切作用，并评估白藜芦醇对再灌注脑的有益作用。我们的研究表明，缺氧-复氧（HR）损伤导致N2a细胞凋亡，并且此过程受到线粒体功能障碍的高度影响。在经过HR处理的N2a细胞中，线粒体膜电位降低，线粒体氧化应激增加和线粒体细胞凋亡通路被激活。有趣的是，白藜芦醇治疗可以通过维持线粒体体内稳态来减轻N2a细胞凋亡。进一步，我们发现白藜芦醇通过激活Mfn1相关的线粒体保护系统来调节线粒体的性能。降低Mfn1可以消除白藜芦醇对HR治疗的N2a细胞的有益作用。此外，我们还报道了白藜芦醇通过AMPK途径调节Mfn1表达。AMPK通路的抑制作用还可以中和白藜芦醇对脑IRI的N2a细胞的抗凋亡作用。综上所述，我们的结果表明线粒体损伤与脑IRI的发展密切相关。此外，我们还证明了白藜芦醇对再灌注脑的保护作用，并表明该作用是通过激活AMPK-Mfn1途径实现的。降低Mfn1可以消除白藜芦醇对HR治疗的N2a细胞的有益作用。此外，我们还报道了白藜芦醇通过AMPK途径调节Mfn1表达。AMPK通路的抑制作用还可以中和白藜芦醇对脑IRI的N2a细胞的抗凋亡作用。综上所述，我们的结果表明线粒体损伤与脑IRI的发展密切相关。此外，我们还证明了白藜芦醇对再灌注脑的保护作用，并表明该作用是通过激活AMPK-Mfn1途径实现的。降低Mfn1可以消除白藜芦醇对HR治疗的N2a细胞的有益作用。此外，我们还报道了白藜芦醇通过AMPK途径调节Mfn1表达。AMPK通路的抑制作用还可以中和白藜芦醇对脑IRI的N2a细胞的抗凋亡作用。综上所述，我们的结果表明线粒体损伤与脑IRI的发展密切相关。此外，我们还证明了白藜芦醇对再灌注脑的保护作用，并表明该作用是通过激活AMPK-Mfn1途径实现的。AMPK通路的抑制作用还可以中和白藜芦醇对脑IRI的N2a细胞的抗凋亡作用。综上所述，我们的结果表明线粒体损伤与脑IRI的发展密切相关。此外，我们还证明了白藜芦醇对再灌注脑的保护作用，并表明该作用是通过激活AMPK-Mfn1途径实现的。AMPK通路的抑制作用还可以中和白藜芦醇对脑IRI的N2a细胞的抗凋亡作用。综上所述，我们的结果表明线粒体损伤与脑IRI的发展密切相关。此外，我们还证明了白藜芦醇对再灌注脑的保护作用，并表明该作用是通过激活AMPK-Mfn1途径实现的。