中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (29): 6228-6238.doi: 10.12307/2025.767

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

督脉电针抑制铁死亡促进急性颈髓损伤模型大鼠的神经修复

孙荣妍1,许卢春2,姜国正2,宋佳伟2,马昱堃2,范娇娇2,王冠龙2,杨永栋2,俞  兴2   

  1. 1北京市海淀医院,北京市  100080;2北京中医药大学东直门医院,北京市  100700
  • 收稿日期:2024-09-18 接受日期:2024-11-09 出版日期:2025-10-18 发布日期:2025-03-07
  • 通讯作者: 俞兴,博士,教授,主任医师,博士生导师,北京中医药大学东直门医院,北京市 100700 共同通讯作者:杨永栋,博士,副研究员,副主任医师,硕士生导师,北京中医药大学东直门医院,北京市 100700
  • 作者简介:第一作者:孙荣妍,1986年生,北京市人,汉族,北京市海淀医院中医科主治医师,主要从事中西医结合促进神经系统损伤修复再生方面的基础和临床研究。 共同第一作者:许卢春,1995年生,江西省南昌市人,汉族,北京中医药大学东直门医院在读博士,主要从事脊柱外科、脊髓损伤方面的研究。
  • 基金资助:
    中央高校基本科研业务费(2024-JYB-JBZD-065),项目负责人:杨永栋;国家自然科学基金面上项目(81973882),项目负责人:俞兴;国家自然科学基金青年项目(81804119),项目负责人:杨永栋;北京中医药大学东直门医院人才培养计划(DZMG-QNGG0010),项目负责人:杨永栋

Du Meridian electroacupuncture inhibits ferroptosis and promotes neurorepair in rats with acute cervical spinal cord injury 

Sun Rongyan1, Xu Luchun2, Jiang Guozheng2, Song Jiawei2, Ma Yukun2, Fan Jiaojiao2, Wang Guanlong2, Yang Yongdong2, Yu Xing2   

  1. 1Haidian Hospital of Beijing, Beijing 100080, China; 2Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
  • Received:2024-09-18 Accepted:2024-11-09 Online:2025-10-18 Published:2025-03-07
  • Contact: Yu Xing, MD, Professor, Chief physician, Doctoral supervisor, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China​ Co-corresponding author: Yang Yongdong, MD, Associate researcher, Associate chief physician, Master’s supervisor, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
  • About author:Sun Rongyan, Attending physician, Haidian Hospital of Beijing, Beijing 100080, China Xu Luchun, Doctoral candidate, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China Sun Rongyan and Xu Luchun contributed equally to this article.
  • Supported by:
    Fundamental Research Funds for the Central Universities, No. 2024-JYB-JBZD-065 (to YYD); National Natural Science Foundation of China (General Program), No. 81973882 (to YX); National Natural Science Foundation of China (Youth Program), No. 81804119 (to YYD); Talent Training Program of Dongzhimen Hospital of Beijing University of Chinese Medicine, No. DZMG-QNGG0010 (to YYD)

摘要:

文题释义:
督脉电针:是在督脉上的特定穴位进行针刺,并在针刺的基础上施加低频电流刺激这些穴位,以促进气血运行,调节中枢神经系统的功能。该方法常用于治疗脊柱相关疾病、神经系统功能障碍及疼痛管理,在临床实践中被广泛应用,具有良好的疗效。
铁死亡:是一种依赖铁的非凋亡性细胞死亡形式,由细胞内铁离子过度积累引发的脂质过氧化反应所导致,这种细胞死亡机制在神经系统疾病、癌症、缺血再灌注损伤等多种病理状态中发挥重要作用,通过调控铁死亡相关的代谢途径,可以为这些疾病的治疗提供新的思路。

背景:近年来,多项研究证实督脉电针在减轻脊髓损伤方面有独特的效果,需进一步明确相关机制。
目的:探讨督脉电针对大鼠颈髓损伤后铁死亡的调节作用及作用机制。
方法:将100只SD大鼠随机分为假手术组、模型组、督脉电针组、RSL3组和督脉电针+RSL3组。假手术组仅切除椎板,其他4组通过Allen法构建急性颈髓损伤模型,督脉电针组在颈髓损伤后给予电针治疗,RSL3组在颈髓损伤后接受谷胱甘肽过氧化物酶4抑制剂RSL3腹腔注射,督脉电针+RSL3组在颈髓损伤后予以督脉电针以及RSL3腹腔注射。术后7,28 d取材,观察大鼠运动功能、组织学形态、神经元存活、胶质瘢痕形成、氧化应激水平、Fe2+含量以及谷胱甘肽过氧化物酶4和长链酰基辅酶A合成酶4表达。
结果与结论:①最终90只大鼠完成后续实验,每组18只;②督脉电针组大鼠的FLS评分和BBB评分显著高于模型组和督脉电针+RSL3组(P < 0.05);③与模型组相比,督脉电针组可以改善颈髓组织学形态和线粒体微观形态,而RSL3逆转了督脉电针对线粒体的保护作用;④与模型组相比,督脉电针组微管相关蛋白2、谷胱甘肽过氧化物酶4、谷胱甘肽和超氧化物歧化酶表达显著增加(P < 0.05),胶质纤维酸性蛋白、长链酰基辅酶A合成酶4、活性氧、丙二醛和Fe2+含量显著减少(P < 0.05),而RSL3逆转了督脉电针对铁死亡、脂质过氧化和氧化应激的抑制作用;⑤结果表明,督脉电针可以通过调控谷胱甘肽过氧化物酶4/长链酰基辅酶A合成酶4轴抑制铁死亡,从而减少颈髓损伤后神经元继发性损伤及胶质瘢痕形成,改善神经功能。
https://orcid.org/0009-0003-8303-896X(孙荣妍)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 颈髓损伤, 督脉电针, 铁死亡, 谷胱甘肽过氧化物酶4, 长链酰基辅酶A合成酶4, 氧化应激, 神经修复, 工程化组织构建

Abstract: BACKGROUND: Recent studies have shown that Du Meridian electroacupuncture has a unique effect on alleviating spinal cord injury, but the underlying mechanisms require further clarification.
OBJECTIVE: To investigate the regulatory effects and the associated action mechanisms of Du Meridian electroacupuncture on ferroptosis after cervical spinal cord injury in rats. 
METHODS: One hundred SD rats were randomly divided into sham, model, Du Meridian electroacupuncture, RSL3, and Du Meridian electroacupuncture + RSL3 groups. The sham group underwent only laminectomy. The other four groups were subjected to cervical spinal cord injury by the Allen method. The Du Meridian electroacupuncture group received electroacupuncture after cervical spinal cord injury. The RSL3 group received intraperitoneal injections of glutathione peroxidase 4 inhibitor RSL3 after cervical spinal cord injury. The Du Meridian electroacupuncture + RSL3 group received both electroacupuncture and RSL3 intervention after cervical spinal cord injury. Samples were collected on postoperative days 7 and 28 to assess motor function, histological morphology, neuronal survival, glial scar formation, oxidative stress levels, Fe2+ content, glutathione peroxidase 4, and long-chain acyl-CoA synthetase 4 expression. 
RESULTS AND CONCLUSION: (1) Finally, 90 rats completed the follow-up experiment, with 18 rats in each group. (2) FLS and BBB scores were significantly higher in the Du Meridian electroacupuncture group compared with the model and Du Meridian electroacupuncture + RSL3 groups (P < 0.05). (3) Compared with the model group, Du Meridian electroacupuncture improved cervical spinal cord tissue morphology and mitochondrial ultrastructure, while these effects were inhibited by RSL3. (4) Du Meridian electroacupuncture increased the expression of microtubule-associated protein 2, glutathione peroxidase 4, glutathione, and superoxide dismutase (P < 0.05) and reduced the expression of glial fibrillary acidic protein, long-chain acyl-CoA synthetase 4, reactive oxygen species, malondialdehyde, and Fe2+ compared with the model group (P < 0.05). However, RSL3 reversed the inhibitory effects of Du Meridian electroacupuncture on ferroptosis, lipid peroxidation and oxidative stress. (5) The results suggest that Du Meridian electroacupuncture inhibits ferroptosis by regulating the glutathione peroxidase 4/long-chain acyl-CoA synthetase 4 axis, thereby reducing secondary neuronal damage and glial scar formation after cervical spinal cord injury and improving neurological function.

Key words: cervical spinal cord injury, Du Meridian electroacupuncture, ferroptosis, glutathione peroxidase 4, long-chain acyl-CoA synthetase 4, oxidative stress, neurorepair, engineered tissue construction

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