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Title: Electroacupuncture improves cognitive dysfunction in rats with Alzheimer's disease by regulating microglial cells.
Author: Li Z, Li MX, Qin YP, Tang W.
Journal: Zhen Ci Yan Jiu; 2023 Nov 25; 48(11):1069-1078. PubMed ID: 37984903.
Abstract:
OBJECTIVES: To observe the effect of electroacupuncture (EA) on microglia (MG), Janus kinase-2 (JAK2) and signal transducer and activator of transcription-3 (STAT3) in hippocampal CA1 region of Alzheimer's di-sease (AD) rats, so as to explore its mechanisms in the treatment of AD. METHODS: Thirty-six male SD rats were randomly divided into sham operation, model and EA groups, with 12 rats in each group. The AD rat model was established by intraperitoneal injection of D-galactose combined with intrahippocampal injection of aggregated Aβ_25-35. The rats in the EA group were given EA (2 Hz/20 Hz, 2 mA) at "Baihui"(GV20) and"Shenting"(GV24) for 30 min, once daily, 6 days a week for 4 weeks. Morris water maze test was used to detect the learning and memory ability and spatial exploration ability of rats. HE staining was used to observe the pathological changes of hippocampus. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The positive expression of MG marker io-nized calcium adaptor protein (Iba-1) in hippocampus was observed by immunofluorescence staining. The expression levels of serum inflammatory factor interferon-γ (IFN-γ) and transforming growth factor beta 1 (TGF-β1) were detected by ELISA. The mRNA expression levels of JAK2, STAT3, inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in hippocampal CA1 region were detected by real-time quantitative PCR. The protein and phosphorylation levels of JAK2 and STAT3 in hippocampal CA1 region were detected by Western blot. RESULTS: Compared with the sham operation group, the escape latency of the model group was significantly prolonged (P<0.01), and the number of crossing the original platform was significantly reduced (P<0.01), the positive expression of Iba-1 in CA1 region, the content of serum IFN-γ, the relative mRNA expressions of JAK2, STAT3 and iNOS, and the protein and phosphorylation levels of JAK2 and STAT3 were significantly increased (P<0.01), while the content of serum TGF-β1 and the relative expression of Arg-1 mRNA were significantly decreased (P<0.01). Compared with the model group, the escape latency of rats in the EA group was significantly shortened (P<0.01), the number of crossing the original platform was significantly increased (P<0.01), the positive expression of Iba1, the content of serum IFN-γ, the mRNA expressions of JAK2, STAT3 and iNOS, and the protein and phosphorylation levels of JAK2 and STAT3 were significantly decreased (P<0.05, P<0.01), while the content of serum TGF-β1 and the expression of Arg-1 mRNA were significantly increased (P<0.01). Moreover, pathological and ultrastructural observation showed a reduction in the number of hippocampal neurons, changement of nuclear morphology, dilation of intercellular space, and decreased number of mitochondria in the model group；these situations were relatively milder in the EA group. CONCLUSIONS: EA can improve the learning and memory function of AD rats, which may be associated with its functions in decreasing MG activities, and inhibiting the JAK2 / STAT3 signaling pathway in the hippocampus. 目的: 观察电针对阿尔茨海默病（AD）大鼠海马CA1区小胶质细胞（MG）及Janus激酶-2（JAK2）、信号转导和转录激活因子-3（STAT3）的影响，探讨电针治疗AD的可能作用机制。方法: SD大鼠随机分为假手术组、模型组和电针组，每组12只。腹腔注射D-半乳糖联合双侧海马内注射聚集态β淀粉样蛋白（Aβ）_25-35制备AD大鼠模型。电针组电针“百会”“神庭”，30 min/次，1次/d，治疗6 d，休息1 d，7 d为1个疗程，共治疗4个疗程。Morris水迷宫实验检测大鼠学习记忆和空间探索能力，HE染色法观察海马CA1区组织病理形态变化，透射电镜观察大鼠海马CA1区神经元超微结构，免疫荧光染色观察大鼠海马MG标记物离子钙接头蛋白1（Iba-1）阳性表达，ELISA法检测大鼠血清γ-干扰素（IFN-γ）、生长转化因子-β1（TGF-β1）含量，实时荧光定量PCR法检测大鼠海马CA1区JAK2、STAT3、诱导型一氧化氮合酶（iNOS）、精氨酸酶-1（Arg-1）mRNA表达水平，Western blot法检测大鼠海马CA1区JAK2、STAT3及其磷酸化蛋白水平。结果: 与假手术组比较，模型组大鼠逃避潜伏期延长（P<0.01），穿越原平台次数减少（P<0.01）；海马神经元数量减少，细胞核形态改变，核膜界限模糊，细胞间隙增大，海马周围神经元出现坏死、空泡变性，细胞核固缩，线粒体数量减少，染色质边集；海马CA1区Iba-1阳性表达升高（P<0.01），血清IFN-γ含量升高（P<0.01）、TGF-β1含量降低（P<0.01），海马CA1区JAK2、STAT3、iNOS mRNA表达升高（P<0.01），Arg-1 mRNA表达降低（P<0.01），JAK2、STAT3及其磷酸化蛋白表达水平升高（P<0.01）。与模型组比较，电针组大鼠逃避潜伏期缩短（P<0.01），穿越原平台次数增加（P<0.01）；海马神经元数量明显增多，结构基本完整，少许细胞核轻度不规则，线粒体少量空泡变形，染色质部分边集；海马CA1区Iba-1阳性表达降低（P<0.05），血清IFN-γ含量降低（P<0.01）、TGF-β1含量升高（P<0.01），海马CA1区JAK2、STAT3、iNOS mRNA表达降低（P<0.01），Arg-1 mRNA表达升高（P<0.01），JAK2、STAT3及其磷酸化蛋白表达水平降低（P<0.01）。结论: 电针“百会”“神庭”能改善AD大鼠学习记忆能力，抑制MG的激活，减少神经炎性因子的释放，延缓神经炎性反应的发生发展，其作用机制可能与抑制脑内JAK2/STAT3信号通路有关。.

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