Attending Physician, Faculty of Life Science and Biotechnology, Kunming University of Science and Technology, P.R. China.
Associate Chief Physician, Department of Neurology, The Affiliated Hospital of Kunming University of Science and Technology, P.R. China.
Scott Med J. 2021 Feb;66(1):16-22. doi: 10.1177/0036933020961543. Epub 2020 Sep 29.
The neurological damage caused by cardiac arrest (CA) can seriously affect quality of life. We investigated the effect of metformin pretreatment on brain injury and survival in a rat CA/cardiopulmonary resuscitation (CPR) model.
After 14 days of pretreatment with metformin, rats underwent 9 minutes of asphyxia CA/CPR. Survival was evaluated 7 days after restoration of spontaneous circulation; neurological deficit scale (NDS) score was evaluated at days 1, 3, and 7. Proteins related to the endoplasmic reticulum (ER) stress response and autophagy were measured using immunoblotting. Seven-day survival was significantly improved and NDS score was significantly improved in rats pretreated with metformin. Metformin enhanced AMPK-induced autophagy activation. AMPK and autophagy inhibitors removed the metformin neuroprotective effect. Although metformin inhibited the ER stress response, its inhibitory effect was weaker than 4-PBA.
In a CA/CPR rat model, 14-day pretreatment with metformin has a neuroprotective effect. This effect is closely related to the activation of AMPK-induced autophagy and inhibition of the ER stress response. Long-term use of metformin can reduce brain damage following CA/CPR.
心脏骤停 (CA) 引起的神经损伤会严重影响生活质量。我们研究了二甲双胍预处理对 CA/心肺复苏 (CPR) 大鼠模型中脑损伤和存活率的影响。
经过 14 天的二甲双胍预处理后，大鼠经历了 9 分钟的窒息性 CA/CPR。自主循环恢复后 7 天评估存活率；在第 1、3 和 7 天评估神经功能缺损评分 (NDS)。使用免疫印迹法测量与内质网 (ER) 应激反应和自噬相关的蛋白质。与未接受预处理的大鼠相比，接受二甲双胍预处理的大鼠的 7 天存活率显著提高，NDS 评分也显著改善。二甲双胍增强了 AMPK 诱导的自噬激活。AMPK 和自噬抑制剂消除了二甲双胍的神经保护作用。虽然二甲双胍抑制了 ER 应激反应，但抑制作用弱于 4-PBA。
在 CA/CPR 大鼠模型中，14 天的二甲双胍预处理具有神经保护作用。这种作用与 AMPK 诱导的自噬激活和 ER 应激反应的抑制密切相关。长期使用二甲双胍可减轻 CA/CPR 后的脑损伤。
