| 卢苑蓉,刘隽阳,郭 婕,李 华,王 渊,赵颖倩,李 杰,王 强.电针早期干预对肌萎缩侧索硬化症小鼠大脑皮层TDP-43及HMGB1/RhoA信号通路的影响[J].中国康复医学杂志,2024,(3):312~319 |
| 电针早期干预对肌萎缩侧索硬化症小鼠大脑皮层TDP-43及HMGB1/RhoA信号通路的影响 点此下载全文 |
| 卢苑蓉 刘隽阳 郭 婕 李 华 王 渊 赵颖倩 李 杰 王 强 |
| 陕西中医药大学第二临床医学院， 陕西省咸阳市，712046 |
| 基金项目：国家自然科学基金项目（82074555）；陕西省教育厅项目（21JS022） |
| DOI：10.3969/j.issn.1001-1242.2024.03.002 |
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| 摘要： |
| 摘要
目的：观察电针早期干预对肌萎缩侧索硬化症（amyotrophic lateral sclerosis，ALS）小鼠大脑皮层TARDNA结合蛋白43（TARDNA binding protein，TDP-43）及HMGB1/RhoA信号通路表达的影响，探究电针早期干预改善ALS小鼠运动功能的潜在机制。
方法：符合SOD1G93A基因表型小鼠按随机数字表法分为模型组（SOD1G93A）、针刺干预组（electroacupuncture， EA）、利鲁唑组（Riluzole），同窝SOD1G93A阴性小鼠为空白对照组（control），每组15只。电针组针刺干预百会穴、双侧天柱穴、双侧天枢穴，5次/7d，7d为一个疗程，共治疗4个疗程。利鲁唑组予利鲁唑30mg/（kg·d）灌胃治疗，１次/d，5次/周，持续2周。采用后肢功能神经学评分和转棒疲劳实验评估各组小鼠运动功能，免疫荧光法观察大脑皮层TDP-43阳性细胞率；Western Blot法检测大脑皮质离子钙结合接头分子1（Iba-1）、HMGB1、RhoA蛋白相对表达量；Elisa法检测血清TNF-α及MCP-1的含量；透射电镜观察大脑皮层神经元形态变化。
结果：与对照组比较，模型组转棒潜伏期时间减少和神经学评分增高（P<0.01），血清MCP-1、TNF-α含量和大脑皮层Iba-1、HMGB1、RhoA蛋白表达以及TDP-43阳性细胞率均升高（P<0.01）。与模型组比较，电针组和利鲁唑组转棒潜伏期时间增加和神经学评分降低（P<0.01，P<0.05），血清MCP-1、TNF-α含量和大脑皮质Iba-1、HMGB1、RhoA蛋白表达以及TDP-43阳性细胞率均降低（P<0.01，P<0.05）。电镜结果显示，对照组小鼠皮层神经元细胞结构正常，模型组小鼠神经细胞有明显病理变化，电针组和利鲁唑组神经细胞损伤减轻，结构较完整，可见部分正常细胞器。
结论：电针干预可改善ALS模型小鼠的运动功能，其机制可能与抑制HMGB1/RhoA信号通路进而减轻小胶质细胞诱导的神经炎症有关，并推测其对于减少ALS病理底物TDP-43的沉积具有正相关作用。 |
| 关键词：肌萎缩侧索硬化症 电针 神经炎症 单核细胞趋化蛋白-1 Ras同源基因家族成员A TARDNA 结合蛋白-43 |
| Effects of early electroacupuncture intervention on TDP-43 and HMGB1/RhoA signaling pathway in cerebral cortex of mice with amyotrophic lateral sclerosis model Download Fulltext |
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| The Second School of Clinical Medicine， Shanxi University of Chinese Medicine， Xianyang， 712046 |
| Fund Project: |
| Abstract: |
| Abstract
Objective： To observe the effect of early electroacupuncture intervention on the expression of TARDNA binding protein 43 （TDP-43） and HMGB1/RhoA signaling pathway in the cerebral cortex of amyotrophic lateral sclerosis （ALS） mice， and to explore the potential mechanism of early electroacupuncture intervention in improving motor function in ALS mice.
Method： SOD1G93A gene phenotype mice were randomly divided into model group （SOD1G93A）， acupuncture intervention group （EA）， riluzole group （Riluzole）， and SOD1G93A negative mice in the same litter were blank control group （Control）， with 15 mice in each group. The electroacupuncture group was given acupuncture of Baihui point， bilateral Tianzhu point， bilateral Tianshu point， 5 times/7 days， 7 days for a course of treatment， a total of 4 courses of treatment. The riluzole group was treated with riluzole 30 mg/（kg·d） by gavage， once a day， five times a week for two weeks. The motor function of mice in each group was evaluated by hind limb functional neurological score and rotarod fatigue test， and the rate of TDP-43 positive cells in cerebral cortex was observed by immunofluorescence. The relative expression of Iba-1， HMGB1 or RhoA protein in cerebral cortex was detected by Western Blot. The levels of serum TNF-α and MCP-1 were detected by Elisa. The morphological changes of cerebral cortical neurons were observed by transmission electron microscopy.
Result： Compared with the control group， the rotarod latency time was decreased and the neurological score was increased in the model group （P<0.01）. The contents of serum MCP-1 and TNF-α， the expression of Iba-1， HMGB1 and RhoA protein in cerebral cortex and the rate of TDP-43 positive cells were increased in the model group （P<0.01）. Compared with the model group， the rotarod latency time of the electroacupuncture group and the riluzole group increased and the neurological score decreased （P<0.01， P<0.05）， the serum MCP-1， TNF-α content and the cerebral cortex Iba-1， HMGB1， RhoA protein expression and TDP-43 positive cell rate decreased （P<0.01， P<0.05）. The results of electron microscopy showed that the structure of cortical neurons in the control group was normal， and the nerve cells in the model group exhibited obvious pathological changes. The damage of nerve cells in the electroacupuncture group and the riluzole group was reduced， the structure was relatively complete， and some normal organelles were detected.
Conclusion： Electroacupuncture intervention can improve the motor function of ALS model mice. The mechanism may be related to the inhibition of HMGB1/RhoA signaling pathway and the reduction of microglia-induced neuroinflammation， and it is speculated that it has a positive effect on the reduction of ALS pathological substrate TDP-43 deposition. |
| Keywords:amyotrophic lateral sclerosis electroacupuncture neuroinflammation monocyte chemotactic protein 1 Ras homolog family member A TARDNA binding protein |
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