PDF(Pubmed)
Abstract：
Ischemic stroke involves various pathological processes, among which ferroptosis is crucial. Previous studies by our group have indicated that electroacupuncture (EA) mitigates ferroptosis after ischemic stroke; however, the precise mechanism underlying this effect remains unclear. In the present study, we developed a rat model of middle cerebral artery occlusion/reperfusion. We chose the main acupoint of the treatment methods of the \"Awakening and Opening of the Brain\". Rats\' neurological function and motor coordination were evaluated by neurological function score and the rotarod test, respectively, and the volume of cerebral infarction was analyzed by 2,3,5-triphenyltetrazolium chloride Staining. The cerebrovascular conditions were visualized by time-of-flight magentic resonance angiography. In addition, we detected changes in lipid peroxidation and endogenous antioxidant activity by measuring the malondialdehyde, glutathione, superoxide dismutase activities, glutathione/oxidized glutathione and reduced nicotinamide adenine dinucleotide phosphate/oxidized nicotinamide adenine dinucleotide phosphate ratios. Inductively coupled plasma-mass spectrometry, western blot, reverse transcription-polymerase chain reaction, fluoro-jade B staining, immunofluorescence analysis, and transmission electron microscopy were utilized to examine the influence of EA. The results indicate that EA treatment was effective in reversing neurological impairment, neuronal damage, and protecting mitochondrial morphology and decreasing the cerebral infarct volume in the middle cerebral artery occlusion/reperfusion rat model. EA reduced iron levels, inhibited lipid peroxidation, increased endogenous antioxidant activity, modulated the expression of several ferroptosis-related proteins, and promoted nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation. However, the protective effect of EA was hindered by the Nrf2 inhibitor ML385. These findings suggest that EA can suppress ferroptosis and decrease damage caused by cerebral ischemia/reperfusion by activating Nrf2 and increasing the protein expression of solute carrier family 7 member 11 and glutathione peroxidase 4.
摘要：
缺血性卒中涉及多种病理过程,其中铁性死亡是至关重要的。我们小组先前的研究表明，电针（EA）可减轻缺血性中风后的铁性凋亡；然而，这种效应的确切机制尚不清楚.在本研究中,我们建立了大鼠大脑中动脉闭塞/再灌注模型。我们选择了“大脑的觉醒和开放”的治疗方法的主要穴位。通过神经功能评分和旋转试验评价大鼠的神经功能和运动协调能力，分别,用氯化2,3,5-三苯基四唑染色分析脑梗死的体积。通过飞行时间磁共振血管造影观察脑血管状况。此外,我们通过测量丙二醛来检测脂质过氧化和内源性抗氧化活性的变化，谷胱甘肽,超氧化物歧化酶活性，谷胱甘肽/氧化型谷胱甘肽和还原型烟酰胺腺嘌呤二核苷酸磷酸/氧化型烟酰胺腺嘌呤二核苷酸磷酸的比例。电感耦合等离子体质谱,westernblot,逆转录聚合酶链反应，荧光玉B染色，免疫荧光分析，和透射电子显微镜用于检查EA的影响。结果表明，EA治疗可有效逆转神经功能缺损，神经元损伤，在大脑中动脉阻塞/再灌注大鼠模型中保护线粒体形态和减少脑梗死体积。EA降低了铁水平，抑制脂质过氧化，增加内源性抗氧化活性，调节几种铁凋亡相关蛋白的表达，并促进核因子-E2相关因子2（Nrf2）的核易位。然而,EA的保护作用受到Nrf2抑制剂ML385的阻碍。这些发现表明，EA可以通过激活Nrf2并增加溶质载体家族7成员11和谷胱甘肽过氧化物酶4的蛋白表达来抑制铁凋亡并减少脑缺血/再灌注引起的损伤。
