中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (19): 3976-3982.doi: 10.12307/2025.043

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

跑台训练激活内源性神经干细胞促进小鼠脊髓损伤的修复

陈婵娟1,2,上官泽宇1,2,李琦哲1,谭  伟1,李  青1   

  1. 1贵州医科大学附属医院创伤骨科,贵州省贵阳市   550004;2贵州医科大学临床医学院,贵州省贵阳市   550025
  • 收稿日期:2023-12-25 接受日期:2024-03-10 出版日期:2025-07-08 发布日期:2024-09-12
  • 通讯作者: 李青,博士,教授,博士生导师,贵州医科大学附属医院创伤骨科,贵州省贵阳市 550004
  • 作者简介:陈婵娟,女,1997年生,贵州省毕节市人,汉族,贵州医科大学在读硕士,主要从事脊柱脊髓损伤康复方面的研究。
  • 基金资助:
    国家自然科学基金项目(82160249,81960234),项目负责人:李青

Treadmill training activates endogenous neural stem cells to promote spinal cord injury repair in mice

Chen Chanjuan1, 2, Shangguan Zeyu1, 2, Li Qizhe1, Tan Wei1, Li Qing1   

  1. Li Qing, PhD, Professor, Doctoral supervisor, Department of Trauma Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
  • Received:2023-12-25 Accepted:2024-03-10 Online:2025-07-08 Published:2024-09-12
  • Contact: Li Qing, PhD, Professor, Doctoral supervisor, Department of Trauma Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
  • About author:Chen Chanjuan, Master candidate, Department of Trauma Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China; School of Clinical Medicine, Guizhou Medical University, Guiyang 550025, Guizhou Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82160249, 81960234 (to LQ)

摘要:

文题释义:

内源性神经干细胞:主要分布在海马、脊髓各节段中央管周围,来源于中枢神经系统,是一种多能神经干细胞,具有自我更新及多向分化潜能,在脊髓损伤后被激活并分化为各种类型的神经细胞,促进内源性修复和神经再生。
跑台训练:又称跑步机训练,是康复训练的主要方法之一,主要用于小鼠或大鼠。跑台装置的核心部分主要由可滚动的传送带构成,传送带的材质有利于动物的足抓地。通道的后方安装有刺激电极和发声装置,作用为当动物停止跑步或跑速低于实验要求时就会碰触到后壁的刺激装置,引发电刺激或声音刺激,使动物继续按照跑台的速度奔跑。

摘要
背景:跑台训练是促进脊髓损伤后运动功能恢复的有效方法之一,可以促进神经发生,但是不同强度跑台训练对脊髓内源性干细胞的激活作用尚不明确。
目的:分析不同强度跑台训练对脊髓损伤后小鼠脊髓内源性神经干细胞的激活作用。
方法:取雌性C57BL/6J小鼠50只,采用随机数字表法分为对照组、脊髓损伤组及低、中、高强度运动组,每组10只。脊髓损伤组及低、中、高强度运动组利用钳夹法构建T10节段脊髓损伤模型,脊髓损伤后第7天,低、中、高强度运动组分别进行对应强度的跑台训练,3次/d,10 min/次,每周训练6次,连续训练28 d。跑台训练后3,7,14,21,28 d,采用BMS评分评估小鼠后肢运动功能;跑台训练后28 d,获取损伤区域脊髓组织,检测细胞激活标志物表皮生长因子受体、静止细胞标志物胶质纤维酸性蛋白、增殖标志物5-乙炔基-2-脱氧尿苷(EdU)表达,苏木精-伊红染色观察脊髓组织形态。

结果与结论:①脊髓损伤各组小鼠BMS评分始终低于对照组(P < 0.05);随着跑台训练时间的延长,脊髓损伤小鼠BMS评分逐渐升高,中强度运动组小鼠跑台训练后14,21 d的BMS评分高于脊髓损伤组及低、高强度运动组(P < 0.05),中、高强度运动组小鼠跑台训练后28 d的BMS评分高于脊髓损伤组、低强度运动组(P < 0.05)。②与对照组比较,脊髓损伤组表皮生长因子受体与EdU阳性细胞比例升高(P < 0.05);与脊髓损伤组比较,低、中、高强度运动组表皮生长因子受体与EdU阳性细胞比例均升高(P < 0.05),并且中强度运动组最高。与对照组比较,脊髓损伤组胶质纤维酸性蛋白阳性细胞比例升高(P < 0.05);与脊髓损伤组比较,低、中、高强度运动组胶质纤维酸性蛋白阳性细胞比例降低(P < 0.05),并且中强度运动组最低。③苏木精-伊红染色显示脊髓损伤组小鼠损伤区域形成大片空洞,不同强度跑台训练后脊髓损伤小鼠损伤区域空洞减小,并且中强度运动组减小最明显。④结果表明,低、中、高强度的跑台训练可通过激活内源性神经干细胞促进脊髓损伤小鼠运动功能的恢复,其中中强度运动训练的效果最明显。

https://orcid.org/0009-0009-4337-3476 (陈婵娟) 


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程


关键词: spinal cord injury, treadmill training, spinal cord neural stem cell, spinal cord endogenous neural stem cell, sports training

Abstract: BACKGROUND: Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury. Treadmill training can promote neurogenesis, but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear.
OBJECTIVE: To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury.
METHODS: Fifty female C57BL/6J mice were divided into control group, spinal cord injury group, low-, moderate-, and high-intensity exercise groups with 10 mice in each group by random number table method. T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group, low-, moderate-, and high-intensity exercise groups. On day 7 after spinal cord injury, mice in the low-, moderate-, and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity, 3 times /d, 10 min/ times, 6 times a week for 28 consecutive days. At 3, 7, 14, 21, and 28 days after treadmill training, the hind limb motor function was evaluated by BMS score. At 28 days after treadmill training, the spinal cord tissue of the injured area was obtained, and the expression of epidermal growth factor receptor, glial fibrillary acidic protein, and 5-Ethynyl-2'-deoxyuridine (EdU), a proliferative marker, was detected. Hematoxylin-eosin staining was used to observe the morphology of spinal cord. 
RESULTS AND CONCLUSION: (1) The BMS score of mice in the spinal cord injury group was lower than that in the control group (P < 0.05). With the extension of treadmill training time, the BMS scores of mice with spinal cord injury gradually increased, and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low- and high-intensity exercise groups (P < 0.05). The BMS score of mice in moderate- and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training (P < 0.05). (2) Compared with the control group, the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group (P < 0.05). Compared with spinal cord injury group, the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-, moderate-, and high-intensity exercise groups (P < 0.05), and the highest was found in moderate-intensity exercise group. Compared with control group, the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group (P < 0.05). Compared with spinal cord injury group, the proportion of glial fibrillary acidic protein positive cells was lower in low-, moderate-, and high-intensity exercise groups (P < 0.05), and the moderate-intensity exercise group was the lowest. (3) Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury, and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training, and the decrease was most obvious in the moderate-intensity exercise group. (4) These results indicate that low-, moderate-, and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells, and the effect of moderate-intensity exercise training is the most obvious.

Key words: 脊髓损伤, 跑台训练, 脊髓神经干细胞, 脊髓内源性神经干细胞, 运动训练

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