针灸推拿医学（英文版）2025，Vol.23Issue(5)：385-393,9.DOI:10.1007/s11726-025-1498-9
电针对肌萎缩侧索硬化症小鼠大脑皮层HMGB1/TLR4通路及少突胶质细胞的影响
Effects of electroacupuncture on the HMGB1/TLR4 pathway and oligodendrocytes in the cerebral cortex of mice with amyotrophic lateral sclerosis
摘要
Abstract
Objective:To explore the effects of early electroacupuncture(EA)intervention on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway-related protein expression and oligodendrocytes in mice with amyotrophic lateral sclerosis(ALS),and uncover the potential molecular mechanisms underlying the improvement of motor function in ALS mice by early EA intervention. Methods:ALS mice carrying the SOD1G93A gene were randomly divided into a model group and an EA group,with 10 mice in each group;10 littermate mice with a negative SOD1G93A genotype served as the control group.In the EA group,Baihui(GV20),Tianzhu(BL10),and Tianshu(ST25)were selected with needles retained for 10 min,5 consecutive days per week,with 2 days of rest.One week constituted a course of treatment,and a total of 3 consecutive courses were performed.The other groups were grasped and fixed similarly,but without intervention.Motor function was assessed using the open field test(OFT)and Morris water maze(MWM).Subsequently,hematoxylin-eosin staining was used to observe neuron morphology in the M1 region of the cerebral cortex.Immunofluorescence was performed to detect the positive cell rate of TAR DNA-binding protein 43(TDP-43),and double immunofluorescence staining was used to observe the positive cell rate and cell states of ionized calcium-binding adaptor molecule 1(Iba-1)and myelin basic protein(MBP)in the M1 region of the cerebral cortex.Western blotting was used to detect the relative expression levels of TDP-43,tumor necrosis factor(TNF)-α,HMGB1,and TLR4 proteins. Results:Compared to the control group,the model group exhibited a reduced total movement distance in the OFT,and an increased escape latency,as well as fewer platform crossings in the MWM,with statistically significant differences(P<0.01).In the model group,the number of degenerated and necrotic neurons in the M1 region of the ALS mouse cerebral cortex increased,with significant nuclear shrinkage and cytoplasmic vacuolization;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex increased(P<0.01),and the relative expression level of TDP-43 protein in the cerebral cortex showed a significant increase(P<0.01);the Iba-1 positive cell percentage increased,while the MBP positive cell percentage decreased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins increased(P<0.05).Compared to the model group,the EA group showed an increased total movement distance(P<0.01),and a reduced escape latency,and more platform crossings in the MWM,with statistically significant differences(P<0.05).In the EA group,neurons showed improvement,with reduced degeneration and necrosis,and larger,clearer nuclei;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex decreased(P<0.05),and the relative expression level of TDP-43 protein also decreased(P<0.05);the percentage of Iba-1 positive cells in the M1 region of the cerebral cortex decreased,while the percentage of MBP positive cells increased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins decreased(P<0.05). Conclusion:EA intervention can suppress microglial activation,improve the state of oligodendrocytes,and reduce abnormal TDP-43 aggregation in the M1 region of the cerebral cortex in ALS model mice;its mechanism of action may be related to the HMGB1/TLR4 signaling pathway.关键词
针刺疗法/电针/肌萎缩侧索硬化症/HMG蛋白质类/Toll样受体4/小胶质细胞/少突神经胶质/小鼠Key words
Acupuncture Therapy/Electroacupuncture/Amyotrophic Lateral Sclerosis/High Mobility Group Proteins/Toll-like Receptor 4/Microglia/Oligodendroglia/Mice分类
医药卫生引用本文复制引用
曾佳玮,赵蔚佳,刘隽阳,刘珊珊,李泐,冯卫星,赵颖倩,王强,姜超..电针对肌萎缩侧索硬化症小鼠大脑皮层HMGB1/TLR4通路及少突胶质细胞的影响[J].针灸推拿医学（英文版）,2025,23(5):385-393,9.基金项目
This work was supported by the Project of National Natural Science Foundation of China(国家自然科学基金项目,No.82074555) （国家自然科学基金项目,No.82074555）
Key Laboratory Project of Education Department of Shaanxi Provincial Government(陕西省教育厅重点实验室项目,No.21JS022). （陕西省教育厅重点实验室项目,No.21JS022）
