Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy
Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy
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Esculetin 通过调节线粒体断裂和线粒体自噬改善小鼠短暂性脑缺血和再灌注引起的认知障碍
DOI：
10.1016/j.bbr.2019.112007
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发表时间：
2019-10
影响因子：
2.7
通讯作者：
Ma Shiping
中科院分区：
文献类型：
--
作者：
Xu Bingru;Zhu Liyang;Chu Jin;Ma Zhanqiang;Fu Qiang;Wei Wei;Deng Xueyang;Ma Shiping
线粒体动力学调节线粒体自噬（mitophagy）和细胞凋亡，这是线粒体和线粒体相关疾病的质量控制的重要事件。七叶壳（ESC）是一种天然香豆素类化合物，在多种动物模型中表现出良好的生物学活性，但其对脑缺血的保护作用尚不清楚。在本文中，我们证明了ESC对短暂性脑缺血和再灌注损伤诱导的小鼠模型的影响，并通过研究线粒体碎片调节的线粒体自噬和凋亡来研究可能的潜在机制。实验结果表明，ESC治疗减轻了短暂性双侧颈总动脉闭塞（tBCCAO）治疗小鼠的神经缺陷，改善了认知障碍。进一步的机制研究表明，tBCCAO可诱导线粒体氧化应激损伤，引发线粒体断裂，表现为丙二醛和线粒体动力蛋白相关蛋白1（Drp 1）水平升高，超氧化物歧化酶和核转录因子E2相关因子2（Nrf 2）活性下调。ESC处理显著减轻了tBCCAO诱导的线粒体应激和线粒体碎片化。此外，线粒体自噬和线粒体凋亡的刺激，在海马的线粒体氧化应激tBCCAO治疗的小鼠，ESC治疗调节线粒体自噬相关因子的表达，包括Bnip 3，Beclin 1，Pink 1，和parkin，LC-3 II/I比，和凋亡相关因子，包括p53，Bax和caspase 3。总之，我们的研究结果表明，ESC治疗调节海马线粒体自噬和线粒体应激引发的线粒体凋亡通过介导的线粒体碎片在短暂的脑缺血和再灌注损伤，这提供了深入了解ESC的潜力，为进一步的治疗意义。
Mitochondrial dynamics regulate mitochondrial autophagy (mitophagy) and apoptosis, which are important events for the quality control of mitochondria and mitochondrial-associated diseases. Esculetin (ESC) is a natural coumarin that exhibits inspiring biological activities in a variety of animal models, but its neuroprotective effects on cerebral ischaemia have not been clearly elucidated. In this paper, we demonstrated the effects of ESC on transient cerebral ischaemia and reperfusion injury induced in a mouse model and examined the possible underlying mechanisms by investigating mitochondrial fragmentation-regulated mitochondrial autophagy and apoptosis. The experimental results showed that ESC treatment alleviated neurological defects and improved cognitive impairments in transient bilateral common carotid artery occlusion (tBCCAO)-treated mice. Further mechanism studies showed that tBCCAO induced mitochondrial oxidative stress injuries and triggered mitochondrial fragmentation, which were evident by the elevated levels of malondialdehyde and mitochondrial dynamin-related protein 1 (Drp1) and the downregulated activities of superoxide dismutase and nuclear transcription factor E2-related factor 2 (Nrf2). ESC treatment significantly alleviated tBCCAO-induced mitochondrial stress and mitochondrial fragmentation. Moreover, mitophagy and mitochondrial apoptosis were stimulated in response to the mitochondrial oxidative stress in the hippocampus of tBCCAO-treated mice, and ESC treatment regulated the expression of mitophagy-related factors, including Bnip3, Beclin1, Pink1, and parkin, the LC-3 II/I ratio, and apoptosis-related factors, including p53, Bax, and caspase 3. Taken together, our results suggest that ESC treatment regulated hippocampal mitophagy and mitochondrial apoptosis triggered by mitochondrial stress via the mediation of mitochondrial fragmentation during transient cerebral ischaemia and reperfusion injury, which provides insight into the potential of ESC for further therapeutic implications.
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影响因子：
21.3
作者：
通讯作者：
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影响因子：
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作者：
Xu W;Jing L;Wang Q;Lin CC;Chen X;Diao J;Liu Y;Sun X
通讯作者：
Sun X
影响因子：
64.5
作者：
Wang, Zhigao;Jiang, Hui;Wang, Xiaodong
通讯作者：
Wang, Xiaodong
影响因子：
5.6
作者：
Chen, Junjun;Deng, Xueyang;Ma, Shiping
通讯作者：
Ma, Shiping
缺氧/缺血应激后线粒体自噬以 Drp1 依赖性方式诱导：抑制 Drp1 在缺血性脑损伤中的作用
影响因子：
4.7
作者：
Zuo, Wei;Zhang, Shuai;Chen, Nai-Hong
通讯作者：
Chen, Nai-Hong