Department of Neurology, The 305 Hospital of the People's Liberation Army, Beijing, China.
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Cell Stress Chaperones. 2023 Nov;28(6):801-809. doi: 10.1007/s12192-023-01372-7. Epub 2023 Aug 22.
In the current investigation, we explored the benefits of aucubin against rodent ischemia/reperfusion (I/R) damages in brains and elucidated the role of 5'-AMP-activated protein kinase (AMPK) in its neuroprotective action. I/R model of brain was established in male three-month-old rats through 2 h of middle cerebral artery occlusion followed by two days of reperfusion. Aucubin boosted phosphorylation of AMPKα in ipsilateral cortex of injured rats. Then, rats were exposed to cerebral I/R damage and received treatment of aucubin and compound C (a well-known AMPK inhibitor). It was found that aucubin administration improved neurological symptom score, decreased infarct volume, and mitigated cerebral edema in injured rats. Aucubin administration upregulated Nrf2 expression and abated oxidative stress in ipsilateral cortex of injured rats. Aucubin administration reduced levels of multiple pro-inflammatory cytokines, suppressed microglial activation and neutrophil infiltration, and promoted M2 polarization in injured rats. More importantly, compound C abolished the neuroprotective, anti-oxidant and inflammation-modulating effects of aucubin in injured rats, at least in part. Therefore, we concluded that activation of AMPK by aucubin alleviated I/R injury in brain through abating oxidative stress and suppressing inflammation, identifying a potential candidate for those patients of ischemic stroke.
在当前的研究中，我们探讨了桃叶珊瑚苷对啮齿动物脑缺血/再灌注（I/R）损伤的益处，并阐明了 5'-AMP 激活的蛋白激酶（AMPK）在其神经保护作用中的作用。通过 2 小时大脑中动脉闭塞和 2 天再灌注，在雄性 3 个月大的大鼠中建立了脑 I/R 模型。桃叶珊瑚苷促进了损伤大鼠对侧皮质中 AMPKα的磷酸化。然后，大鼠暴露于脑 I/R 损伤，并接受桃叶珊瑚苷和化合物 C（一种著名的 AMPK 抑制剂）的治疗。结果发现，桃叶珊瑚苷给药可改善神经症状评分，减少梗死体积，并减轻损伤大鼠的脑水肿。桃叶珊瑚苷给药可上调 Nrf2 表达并减轻损伤大鼠对侧皮质的氧化应激。桃叶珊瑚苷给药可降低多种促炎细胞因子的水平，抑制小胶质细胞激活和中性粒细胞浸润，并促进损伤大鼠的 M2 极化。更重要的是，化合物 C 至少部分消除了桃叶珊瑚苷对损伤大鼠的神经保护、抗氧化和炎症调节作用。因此，我们得出结论，桃叶珊瑚苷通过减轻氧化应激和抑制炎症激活 AMPK 减轻脑 I/R 损伤，为缺血性中风患者提供了一种潜在的候选药物。
