Deletion of mitochondrial uncoupling protein 2 (UCP2) has been shown to aggravate ischemic damage in the brain. However, the underlying mechanisms are not fully understood. The objective of this study is to explore the impact of homozygous UCP2 deletion (UCP2^-/-) on mitochondrial fission and fusion dynamic balance in ischemic mice under normo- and hyperglycemic conditions. UCP2^-/- and wildtype mice were subjected to a 60 min middle cerebral artery occlusion (MCAO) and allowed reperfusion for 6h, 24h and 72h. Our results demonstrated that deletion of UCP2 enlarged infarct volumes and increased numbers of cell death in both normo- and hyperglycemic ischemic mice compared with their wildtype counterparts subjected to the same duration of ischemia and reperfusion. The detrimental effects of UCP deletion were associated with increased ROS production, elevated mitochondrial fission markers Drp1 and Fis1 and suppressed fusion markers Opa1 and Mfn2 in UCP2^-/- mice. Electron microscopic study demonstrated a marked mitochondrial swolling after 6h of reperfusion in UCP2^-/- mice, contrasting to a mild mitochondrial swolling in wildtype ischemic animals. It is concluded that the exacerbating effects of UCP2^-/- on ischemic outcome in both normo- and hyperglycemic animals are associated with increased ROS production, disturbed mitochondrial dynamic balance towards fission and early damage to mitochondrial ultrastructure.

中文翻译：

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在正常和高血糖条件下，线粒体解偶联蛋白 2 的缺失会加剧遭受脑缺血和再灌注损伤的小鼠的线粒体损伤

已显示线​​粒体解偶联蛋白 2 (UCP2) 的缺失会加重大脑的缺血性损伤。然而，潜在的机制尚不完全清楚。本研究的目的是探讨纯合 UCP2 缺失 (UCP2 ^-/- ) 对正常和高血糖条件下缺血小鼠线粒体裂变和融合动态平衡的影响。UCP2 ^-/-对野生型小鼠进行 60 分钟大脑中动脉闭塞 (MCAO) 并允许再灌注 6 小时、24 小时和 72 小时。我们的研究结果表明，与遭受相同缺血和再灌注持续时间的野生型对应物相比，UCP2 的缺失扩大了正常和高血糖缺血小鼠的梗塞体积和细胞死亡数量。UCP 缺失的不利影响与 UCP2 ^-/-小鼠中 ROS 产生增加、线粒体裂变标志物 Drp1 和 Fis1 升高以及融合标志物 Opa1 和 Mfn2 抑制有关。电子显微镜研究表明，再灌注 6 小时后，UCP2 中有明显的线粒体肿胀^-/-小鼠，与野生型缺血动物的轻度线粒体肿胀形成对比。得出的结论是，UCP2 ^-/-对正常和高血糖动物缺血结果的恶化作用与增加的 ROS 产生、扰乱的线粒体分裂动态平衡和线粒体超微结构的早期损伤有关。