Ischemia/reperfusion cerebral injury can cause serious damage to nerve cells. The injured organelles are cleared by autophagy eventually, which is critical for cell survival. Dexmedetomidine is neuroprotective in various ischemia/reperfusion models. Mitochondrial calcium uniporter (MCU) is the most important channel of mitochondrial Ca2+ influx into mitochondria, where Ca2+ has a potential effect on mitochondrial autophagy. However, the role of MCU in the changes of mitophagy and autophagy caused by dexmedetomidine is unknown. In this study, we constructed an in vitro I/R model by subjecting the oxygen and glucose deprivation/reperfusion model to SH-SY5Y cells to mimic the cerebral I/R injury. We found that postconditioning with dexmedetomidine and 3-methyladenine (3MA, an autophagy inhibitor) increased the cell survival meanwhile reduced the production of autophagic vesicles and the expression of LC3 and Beclin 1. This process also increased the expression of BCL-2, P62, and TOM20. After applied with spermine (MCU-specific agonist), the expression of autophagy proteins by dexmedetomidine was reversed, and the same changes were also observed in immunofluorescence. The results of our study suggested that dexmedetomidine can inhibit MCU and reduce excessive mitophagy and autophagy for conferring protection against I/R injury.

中文翻译：

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右美托咪定在缺血/再灌注损伤中的应用及分析途径。

缺血/再灌注脑损伤会严重损害神经细胞。最终通过自噬清除受伤的细胞器，这对于细胞存活至关重要。右美托咪定在各种缺血/再灌注模型中具有神经保护作用。线粒体钙单向转运蛋白（MCU）是线粒体Ca2 +流入线粒体的最重要通道，其中Ca2 +对线粒体自噬具有潜在的影响。但是，MCU在右美托咪定引起的线粒体和自噬变化中的作用尚不清楚。在这项研究中，我们通过将氧和葡萄糖的剥夺/再灌注模型置于SH-SY5Y细胞中以模拟脑I / R损伤，从而构建了体外I / R模型。我们发现，使用右美托咪定和3-甲基腺嘌呤（3MA，（自噬抑制剂）增加细胞存活率，同时减少自噬囊泡的产生以及LC3和Beclin 1的表达。该过程还增加了BCL-2，P62和TOM20的表达。施用精胺（MCU特异性激动剂）后，右美托咪定逆转了自噬蛋白的表达，并且在免疫荧光中也观察到了相同的变化。我们的研究结果表明，右美托咪定可以抑制MCU并减少过多的自噬和自噬，从而提供针对I / R损伤的保护作用。免疫荧光也观察到相同的变化。我们的研究结果表明，右美托咪定可以抑制MCU并减少过多的自噬和自噬，从而提供针对I / R损伤的保护作用。免疫荧光也观察到相同的变化。我们的研究结果表明，右美托咪定可以抑制MCU并减少过多的自噬和自噬，从而提供针对I / R损伤的保护作用。