To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on amyotrophic lateral sclerosis (ALS) in mouse models based on myeloid cell trigger receptor 2 (TREM2)-mediated microglial activation. Thirty-six SPF-grade male human mutant superoxide dismutase 1 (SOD1-G93A) transgenic mice were divided into a model group, an EA group, and a drug group, 12 mice in each group. Besides, 12 wide-type littermates were collected as a control group. In the EA group, EA was performed at the "Zusanli" (ST36), with an intermittent wave, at the frequency of 15 Hz, and for 10 min each intervention; once every other day, 3 interventions a week and for 4 continuous weeks. In the drug group, the intragastric administration of riluzole solution was given at 8 mg/kg, once daily, for 4 continuous weeks. After intervention completion, behavioral assessment of mice was conducted using rotarod test and wire hang test. With HE and Nissl staining adopted, morphology of motor neurons in the anterior horn of the spinal cord was observed. Immunofluorescence was used to detect the fluorescence intensity of TREM2 in the anterior horn of spinal cord. Western blot analysis was performed to measure the protein expression of interleukin (IL)-1β, γ interferon (IFN-γ), IL-4 and IL-10 in spinal cord tissue. Flow cytometry was used to analyze the proportion of CD86+ and CD206+ in spinal cord monocyte suspension. Compared with the control group, in the model group, motor neurons in the anterior horn of the spinal cord exhibited disordered arrangement; accompanied by nuclear pyknosis and cytoplasmic shrinkage; the latency to fall in the rotarod test and the cut-off time in the wire hang test were shortened, fluorescence intensity of TREM2 in the spinal anterior horn, the protein expression of IL-1β, IFN-γ, IL-4, and IL-10, and the proportion of CD86+ and CD206+ in spinal cord tissue increased(P<0.01). When compared with the model group, in the EA and drug groups, motor neurons in the anterior horn of the spinal cord were arranged regularly; nuclear pyknosis and chromatolysis were attenuated, and the structural integrity of neurons was improved; the latency to fall and the the cut-off time were prolonged, fluorescence intensity of TREM2 in the spinal anterior horn was reduced, the protein expression of IL-1β and IFN-γ decreased, and that of IL-4, and IL-10 increased in the spinal cord tissue; the proportion of CD86+ in spinal cord tissue was reduced and that of CD206+ elevated(P<0.01, P<0.05). Compared with the drug group, the EA group showed the increase of protein expression of IL-1β,and the decrease of IL-4, IL-10 in the spinal cord tissue and the proportion of CD206+ (P<0.05). Electroacupuncture at "Zusanli" (ST36) exhibits a certain improvements in motor function of SOD1-G93A transgenic mice. The underlying mechanism may be related to attenuating neuroinflammation via the modulation of microglial activation mediated by TREM2. 目的：基于髓样细胞触发受体2（TREM2）介导的小胶质细胞活化观察电针“足三里”对肌萎缩侧索硬化症模型小鼠神经炎症的影响。 方法：将36只SPF级雄性人突变型超氧化物歧化酶1（SOD1-G93A）转基因小鼠随机分为模型组、电针组、药物组，每组12只；选取12只同窝野生小鼠作为对照组。电针组于“足三里”进行电针干预，采用断续波，频率15 Hz，每次10 min，隔日1次，每周3次，共4周；药物组予利鲁唑溶液（8 mg/kg）灌胃，每日1次，共4周。干预结束后，应用转棒测试与钢丝悬挂测试评估各组小鼠行为学，HE染色和尼氏染色观察各组小鼠脊髓前角运动神经元形态，免疫荧光法检测各组小鼠脊髓前角TREM2荧光强度，Western blot法检测各组小鼠脊髓组织白细胞介素（IL）-1β、γ干扰素（IFN-γ）、IL-4、IL-10蛋白表达，流式细胞术检测各组小鼠脊髓组织单细胞悬液CD86+和CD206+细胞比例。 结果：与对照组比较，模型组小鼠脊髓前角运动神经元排列紊乱，出现核固缩、胞体皱缩等现象；转棒测试潜伏期和钢丝悬挂测试掉落时间缩短，脊髓前角TREM2荧光强度升高，脊髓组织IL-1β、IFN-γ、IL-4、IL-10蛋白表达升高，脊髓组织单细胞悬液CD86+、CD206+细胞比例升高（P<0.01）。与模型组比较，电针组和药物组小鼠脊髓前角运动神经元排列较规整，核固缩及尼氏小体溶解丢失现象改善，神经元结构完整性提高；转棒测试潜伏期和钢丝悬挂测试掉落时间延长，脊髓前角TREM2荧光强度降低，脊髓组织IL-1β、IFN-γ蛋白表达降低，IL-4、IL-10蛋白表达升高，脊髓组织CD86+细胞比例降低，CD206+细胞比例升高（P<0.01，P<0.05）。与药物组比较，电针组脊髓组织IL-1β蛋白表达升高，IL-4、IL-10蛋白表达降低，CD206+细胞比例降低（P<0.05）。 结论：电针“足三里”对SOD1-G93A转基因小鼠运动功能具有一定的改善作用，其作用机制可能为调控TREM2介导的小胶质细胞活化，进而改善神经炎症。.
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PubMed · 2026-05-12
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