针刺研究

2021, v.46(05) 353-361

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电针对阿尔茨海默病小鼠海马与脾脏相关炎性因子表达的影响
Effect of electroacupuncture on learning-memory ability and expression of IL-1β, IL-6 and TNF-α in hippocampus and spleen in mice with Alzheimer’s disease

杨佳一;姜婧;田会玲;汪子栋;任菁钰;刘浩;李志刚;
YNAG Jia-Yi;JIANG Jing;TIAN Hui-ling;WANG Zi-Dong;REN Jing-yu;LIU Hao;LI Zhi-gang;School of Acupunc-ture-moxibustion and Tuina,Beijing University of Chinese Medicine;School of Nursing,Beijing University of Chinese Medicine;

摘要(Abstract):

目的:通过观察小鼠空间学习记忆能力,海马神经元及脾淋巴细胞形态及数目,白介素(IL)-1β、IL-6及TNF-α在海马与脾中的表达情况,探讨电针对阿尔茨海默病(AD)小鼠的作用机制。方法:将24只SAMP8小鼠随机分为电针组、药物组、模型组,每组8只,另以8只SAMR1小鼠为正常组。电针组电针"百会""印堂",留针20 min/d, 1次/d,共15 d;药物组灌胃给药(盐酸多奈哌齐0.92 mg/kg)治疗,1次/天,共15 d。用Morris水迷宫观察各组小鼠行为学变化;称量并比较各组小鼠脾脏质量,计算脾指数;HE染色法观察各组小鼠海马神经元形态及脾脏淋巴细胞数目变化;免疫组织化学法检测各组小鼠海马与脾脏IL-1β、IL-6及肿瘤坏死因子(TNF)-α的阳性表达;Western blot法检测各组小鼠海马与脾脏IL-1β、IL-6及TNF-α的蛋白相对表达量。结果:与正常组比较,模型组小鼠的逃避潜伏期明显延长(P<0.05,P<0.01),脾指数升高(P<0.01),海马区神经元排列相对混乱,部分神经元呈现细胞核固缩或凋亡状态,脾脏被膜组织增厚肿胀、结构疏松,远离被膜处淋巴细胞数量相对增多,海马CA3区及脾脏的IL-1β、IL-6及TNF-α阳性表达及蛋白相对表达量均明显升高(P<0.01,P<0.05)。与模型组比较,电针组第5天逃避潜伏期时间明显缩短(P<0.01),电针组及药物组脾脏指数均明显降低(P<0.01),海马神经元及脾淋巴细胞状态明显改善,海马与脾脏IL-1β、IL-6及TNF-α阳性表达及蛋白相对表达量明显降低(P<0.01,P<0.05)。与药物组比较,电针组逃避潜伏期明显缩短(P<0.01),脾脏指数明显降低(P<0.01),海马区IL-6、脾脏TNF-α阳性表达明显降低(P<0.01,P<0.05)。结论:电针可提高AD小鼠学习记忆能力,改善海马与脾的炎性反应状况。
Objective To explore the effect of electroacupuncture(EA) on the ability of spatial learning-memory and the expression of IL-1β, IL-6 and TNF-α in the hippocampus and spleen tissues and the number of hippocampal neurons and spleen lymphocytes in Alzheimer's disease(AD) mice, so as to study its mechanisms underlying improvement of AD. Methods Twenty-four SAMP8 mice were randomly and equally divided into AD model, EA and medication groups, and 8 SAMR1 mice were used as the control group. EA(2 Hz, 0.1 mA) was applied to "Baihui"(GV20) and "Yintang"(EX-HN3) for 20 min in the EA group, and intragastric administration of donepezil hydrochloride(0.92 mg/kg) was applied in the medication group, once daily for 15 d. The learning-memory ability was determined by Morris water maze task, and the histopathological changes of hippocampus were observed after H.E. staining, followed by determining neurons and the number of splenic lymphocytes. The expression levels of IL-1β, IL-6 and TNF-α in the hippocampus and spleen were detected by immunohistochemistry and Western blot, respectively. Results After mode-ling, the escape latency of place navigation test in the Morris water maze, the spleen index, immunoactivity and expression levels of IL-1β, IL-6 and TNF-α proteins in the hippocampus and spleen tissues were significantly increased(P<0.05, P<0.01). Compared with the model group, the escape latency, spleen index, immunoactivity and expression levels of IL-1β, IL-6 and TNF-α proteins in both hippocampus and spleen were significantly down-regulated in the medication(except the escape latency) and EA groups(P<0.01, P<0.05). The effect of EA was evidently superior to that of medication in shortening the escape latency, lowering the spleen index, and immunoactivity of hippocampal IL-6 and splenic TNF-α immunoactivity(P<0.01, P<0.05). Outcomes of H.E. staining showed disordered arrangement of neurons with nuclear pyknosis or apoptosis in partial neurons in the hippocampus, and thickened and swollen spleen capsule tissue with loose structure and an increased number of lymphocytes in the model group, which was relatively milder in the EA and medication groups. Conclusion EA can improve the learning-memory ability of AD mice, which may be associated with its effect in relieving the inflammation reaction in the hippocampus and spleen tissues.

关键词(KeyWords): 电针;阿尔茨海默症;学习记忆能力;中枢炎性反应;外周免疫;海马
Electroacupuncture;Alzheimer's disease;Learning-memory ability;Central inflammation;Peripheral immunity;Hippocampus

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金青年项目(No.81804178)

作者(Author): 杨佳一;姜婧;田会玲;汪子栋;任菁钰;刘浩;李志刚;
YNAG Jia-Yi;JIANG Jing;TIAN Hui-ling;WANG Zi-Dong;REN Jing-yu;LIU Hao;LI Zhi-gang;School of Acupunc-ture-moxibustion and Tuina,Beijing University of Chinese Medicine;School of Nursing,Beijing University of Chinese Medicine;

Email:

DOI: 10.13702/j.1000-0607.200980

参考文献(References):

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