| 引用本文: |
李千隽, 魏瑢琪, 刘晓月, 袁嘉, 陈俐彤, 田浩梅, 陈楚淘.针刺通过调控Nrf2、GPX4 mRNA表达抑制铁死亡减轻脑缺血再灌注损伤[J].湖南中医药大学学报,2026,46(6):1129-1135[点击复制] |
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| 针刺通过调控Nrf2、GPX4 mRNA表达抑制铁死亡减轻脑缺血再灌注损伤 |
| 李千隽,魏瑢琪,刘晓月,袁嘉,陈俐彤,田浩梅,陈楚淘 |
| (湖南中医药大学针灸推拿与康复学院, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨针刺干预调控核因子E2相关因子2（Nrf2）、谷胱甘肽过氧化物酶4（GPX4） mRNA表达对脑缺血再灌注损伤（CIRI）大鼠神经细胞铁死亡的影响，探究针刺治疗CIRI的可能作用机制。方法 采用随机数字表法将60只雄性SD大鼠分为假手术组（20只）、造模组（40只）。造模组通过构建大脑中动脉闭塞再灌注（MCAO/R）模型，模拟缺血再灌注损伤病理过程，造模成功后再随机分为模型组与针刺组，每组20只。针刺组捆绑并针刺大椎、百会、水沟穴，每次留针30 min；假手术组与模型组只捆绑不针刺。以上各组每12 h干预1次，共干预7次。干预前后，采用改良Garcia评分对大鼠的神经功能受损状况进行评估；干预后，采用TTC染色法对脑组织梗死区域的体积占比进行测定，采用RT-qPCR法检测缺血半暗带区脑组织Nrf2与GPX4 mRNA表达水平，采用比色法、ELISA法检测铁离子（Fe2+）、活性氧（ROS）含量变化，采用TBA法、微板法检测丙二醛（MDA）、谷胱甘肽（GSH）含量变化。结果 干预后，与假手术组相比，模型组神经功能评分显著降低（P<0.01），脑梗死体积比显著增大（P<0.01），Nrf2 mRNA表达显著上调、GPX4 mRNA表达显著下调（P<0.01），Fe2+、ROS、MDA含量显著升高（P<0.01），GSH含量显著降低（P<0.01）。干预后，与模型组相比，针刺组神经功能评分显著升高（P<0.01），脑梗死体积比显著缩小（P<0.01），Nrf2、GPX4 mRNA表达显著上调（P<0.01），Fe2+、ROS、MDA含量下降（P<0.05，P<0.01），GSH含量升高（P<0.05）。结论 针刺可通过上调Nrf2 mRNA表达，促进其下游靶基因GPX4 mRNA表达，改善CIRI大鼠神经功能缺损，缩小脑梗死体积，减少铁过载和ROS生成，抑制脂质过氧化，从而发挥脑保护作用。 |
| 关键词: 脑缺血再灌注损伤 针刺 核因子E2相关因子2 谷胱甘肽过氧化物酶4 铁死亡 缺血半暗带 神经功能缺损 |
| DOI：10.3969/j.issn.1674-070X.2026.06.005 |
| 投稿时间：2026-03-19 |
| 基金项目:国家自然科学基金项目（82274662）；湖南省研究生科研创新课题（2025CX066）。 |
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| Acupuncture alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis via regulating the mRNA expression of Nrf2 and GPX4 |
| LI Qianjun, WEI Rongqi, LIU Xiaoyue, YUAN Jia, CHEN Litong, TIAN Haomei, CHEN Chutao |
| (School of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the effects of acupuncture intervention on neuronal ferroptosis in rats with cerebral ischemia-reperfusion injury (CIRI) by regulating the mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4), and to explore the possible mechanism of action of acupuncture in treating CIRI. Methods A total of 60 male SD rats were randomly divided into sham-operated group (n=20) and modeling group (n=40) using random number table. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in rats of the modeling group to mimic the pathological process of ischemia-reperfusion injury. After successful modeling, the modeling group was further randomly divided into model group and acupuncture group with 20 rats in each group. Rats in the acupuncture group were immobilized and treated with acupuncture at Dazhui (GV14), Baihui (GV20), and Shuigou (GV26) with needles retained for 30 mins each time; rats in the sham-operated group and model group were only immobilized without acupuncture. All groups received intervention once every 12 hours for a total of 7 sessions. Before and after the intervention, neurological deficits were assessed using the modified Garcia score. After the intervention, the volume proportion of cerebral infarct area was measured by TTC staining. The mRNA expression levels of Nrf2 and GPX4 in brain tissues of the ischemic penumbra were tested by RT-qPCR. The levels of ferrous ion (Fe2+) and reactive oxygen species (ROS) were determined by colorimetry and ELISA, while the content of malondialdehyde (MDA) and glutathione (GSH) were checked by TBA method and the microplate method. Results After intervention, the model group showed a significant decrease in the neurological function score (P<0.01), a significant increase in the cerebral infarction volume ratio (P<0.01), significant up-regulation of the mRNA expression of Nrf2 and down-regulation of the mRNA expression of GPX4 (P<0.01), a significant increase in the content of Fe2+, ROS and MDA (P<0.01) as well as a significant decrease in the content of GSH (P<0.01), compared with the sham-operated group. After intervention, the acupuncture group presented a significant increase in neurological function score (P<0.01), a significant decrease in cerebral infarction volume ratio (P<0.01), significant up-regulation of the mRNA expression of Nrf2 and GPX4 (P<0.01), as well as a decrease in the levels of Fe2+, ROS and MDA (P<0.05, P<0.01), and an increase in the content of GSH (P<0.05), compared with the model group. Conclusion Acupuncture can exert a cerebral protective effect by up-regulating the mRNA expression of Nrf2, and subsequently promoting the mRNA expression of its downstream target gene GPX4, thereby ameliorating neurological deficits, reducing cerebral infarct volume, alleviating iron overload, suppressing ROS production, and inhibiting lipid peroxidation in rats with CIRI. |
| Key words: cerebral ischemia-reperfusion injury acupuncture Nrf2 GPX4 ferroptosis ischemic penumbra neurological deficit |
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