Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei, China; Key Laboratory of Clinical Neurology Ministry of Education, Shijiazhuang, Hebei, China.
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei, China; Key Laboratory of Clinical Neurology Ministry of Education, Shijiazhuang, Hebei, China.
Tissue Cell. 2024 Aug;89:102472. doi: 10.1016/j.tice.2024.102472. Epub 2024 Jul 10.
Cerebral ischemia-reperfusion injury involves a series of pathophysiological processes that occur when blood supply is restored after cerebral vascular obstruction, leading to neuronal damage. The AMPK/ERK1/2 signaling pathway has been identified as crucial in this process, although the exact mechanisms underlying the induction of ischemia-reperfusion injury remain unclear. In this study, we investigated the involvement of the AMPK/ERK1/2 signaling pathway in neuronal oxidative stress damage following cerebral ischemia-reperfusion by establishing animal and cell models. Our experimental results demonstrated that cerebral ischemia-reperfusion leads to oxidative stress damage, including cell apoptosis and mitochondrial dysfunction. Moreover, further experiments showed that inhibition of AMPK and ERK1/2 activity, using U0126 and Compound C respectively, could alleviate oxidative stress-induced cellular injury, improve mitochondrial morphology and function, reduce reactive oxygen species levels, increase superoxide dismutase levels, and suppress apoptosis. These findings clearly indicate the critical role of the AMPK/ERK1/2 signaling pathway in regulating oxidative stress damage and cerebral ischemia-reperfusion injury. The discoveries in this study provide a theoretical basis for further research and development of neuroprotective therapeutic strategies targeting the AMPK/ERK1/2 signaling pathway.
脑缺血再灌注损伤涉及一系列病理生理过程，发生在脑血管阻塞后血液供应恢复时，导致神经元损伤。AMPK/ERK1/2 信号通路已被确定在这个过程中至关重要，尽管诱导缺血再灌注损伤的确切机制仍不清楚。在这项研究中，我们通过建立动物和细胞模型，研究了 AMPK/ERK1/2 信号通路在脑缺血再灌注后神经元氧化应激损伤中的作用。我们的实验结果表明，脑缺血再灌注导致氧化应激损伤，包括细胞凋亡和线粒体功能障碍。此外，进一步的实验表明，分别使用 U0126 和 Compound C 抑制 AMPK 和 ERK1/2 的活性，可以减轻氧化应激诱导的细胞损伤，改善线粒体形态和功能，降低活性氧水平，增加超氧化物歧化酶水平，并抑制细胞凋亡。这些发现清楚地表明，AMPK/ERK1/2 信号通路在调节氧化应激损伤和脑缺血再灌注损伤中起着关键作用。本研究的发现为进一步研究和开发针对 AMPK/ERK1/2 信号通路的神经保护治疗策略提供了理论基础。
