Department of Acupuncture and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu Province, China.
Department of Intensive Care Medicine, Huai'an Hongze District People's Hospital, Huai'an, 223100, Jiangsu Province, China.
Curr Neurovasc Res. 2023;20(3):346-353. doi: 10.2174/1567202620666230623153728.
Electroacupuncture (EA) treatment has been recommended by World Health Organization (WHO) for years on cerebral ischemia treatment, but the specific mechanism is still elusive. Studies have shown that EA can relieve brain damage after ischemic stroke by inhibiting programmed cell death (PCD), such as apoptosis, necroptosis, and autophagy. Ferroptosis, a unique form of cell death, has been highlighted recently and found to occur in I/R injury. We, therefore, investigated whether EA plays an essential role in relieving cerebral I/R injury via ferroptosis.
The modified MCAO/R rats model was established and then divided into four groups with or without EA treatment. Neurological deficit score and TTC staining were used to evaluate the neurological deficit and infarct volume of each group. Transmission electron microscope (TEM) and immunofluorescence staining were applied for mitochondrial ultrastructure and ROS accumulation observation, respectively. The proteins and mRNA expression of ACSL4, TFR1, and GPX4 were assessed by western blot and qPCR to detect the progress of ferroptosis.
EA treatment improved neurological deficits and reduced infarct volume. Moreover, EA significantly relieved the mitochondrial morphological changes and inhibited ROS Production in MCAO rats. In terms of its mechanism, EA obviously decreased the ACSL4 and TFR1 expressions and promoted GPX4 levels in MCAO/R model rats.
These findings indicate that EA might play an essential role in relieving cerebral I/R injury via ferroptosis.
世界卫生组织(WHO)多年来一直推荐电针(EA)治疗脑缺血,但具体机制仍不清楚。研究表明,EA 通过抑制程序性细胞死亡(PCD),如细胞凋亡、坏死性凋亡和自噬,可以减轻缺血性中风后的脑损伤。铁死亡,一种独特的细胞死亡形式,最近受到了关注,并在 I/R 损伤中发现。因此,我们研究了 EA 是否通过铁死亡在缓解脑 I/R 损伤中发挥重要作用。
建立改良 MCAO/R 大鼠模型,然后分为 EA 治疗组和对照组。用神经功能缺损评分和 TTC 染色评估每组的神经功能缺损和梗死体积。透射电子显微镜(TEM)和免疫荧光染色分别用于观察线粒体超微结构和 ROS 积累。用 Western blot 和 qPCR 评估 ACSL4、TFR1 和 GPX4 的蛋白和 mRNA 表达,以检测铁死亡的进展。
EA 治疗改善了神经功能缺损,减少了梗死体积。此外,EA 明显缓解了 MCAO 大鼠的线粒体形态变化,并抑制了 ROS 的产生。在机制方面,EA 明显降低了 MCAO/R 模型大鼠中 ACSL4 和 TFR1 的表达,促进了 GPX4 的水平。
这些发现表明,EA 通过铁死亡在缓解脑 I/R 损伤中可能发挥重要作用。