Wan Fang, Zhuang Kun, Li Ziyu, Wang Xiaoqing, Li Wenyan, Hou Yunlong, You Wanhui, Jiang Yibing, Wang Mingye, Zhu Pengyu
International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.
Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
IBRO Neurosci Rep. 2025 Mar 9;18:432-442. doi: 10.1016/j.ibneur.2025.03.001. eCollection 2025 Jun.
This study investigates the therapeutic effects and mechanisms of electroacupuncture (EA) on cognitive impairment induced by chronic hypoxia (CH) in mice. Chronic hypoxia was simulated by exposing mice to a 10 % oxygen environment for 8 hours daily over 3 months. The cognitive functions of the mice were assessed through behavioral tests, including the open field test (OFT), Y-maze, and Morris water maze (MWM). Results showed that CH induced significant anxiety-like behaviors and memory impairments in mice. EA treatment, targeting the Baihui (GV20), Shenting (GV24), and Zusanli (ST36) acupoints, significantly ameliorated these behavioral deficits. Histological analyses using HE staining, Nissl staining, and TUNEL assays demonstrated that EA reduced neuronal damage, apoptosis, and myelin loss in the cerebral cortex and hippocampus. Additionally, EA treatment significantly lowered the expression of the pro-inflammatory cytokine TNF-α in brain tissues, suggesting its anti-inflammatory effects. Immunofluorescence and Western blot analyses revealed that EA inhibited the overactivation of microglia and astrocytes in the CH model. Specifically, EA suppressed the expression of Iba1 and GFAP, markers of microglial and astrocytic activation, respectively. Furthermore, EA promoted the polarization of microglia towards the M2 anti-inflammatory phenotype by downregulating iNOS and upregulating Arg1. Similarly, EA reduced the expression of C3, a marker of A1 astrocytes, thereby preventing astrocytic polarization towards the pro-inflammatory state. Organotypic brain slice cultures subjected to oxygen-glucose deprivation (OGD) confirmed that electrical stimulation, akin to EA, inhibited the activation of microglia and astrocytes under hypoxic conditions. In conclusion, EA improves cognitive function in CH-induced mice by reducing neuroinflammation, inhibiting glial cell overactivation, and promoting anti-inflammatory phenotypes. These findings highlight EA's potential as a therapeutic intervention for cognitive impairments related to chronic hypoxia.
本研究探讨电针（EA）对小鼠慢性缺氧（CH）所致认知障碍的治疗作用及机制。通过将小鼠每天暴露于10%氧气环境中8小时，持续3个月来模拟慢性缺氧。通过行为学测试评估小鼠的认知功能，包括旷场试验（OFT）、Y迷宫和莫里斯水迷宫（MWM）。结果显示，CH诱导小鼠出现明显的焦虑样行为和记忆障碍。针对百会（GV20）、神庭（GV24）和足三里（ST36）穴位的电针治疗显著改善了这些行为缺陷。使用苏木精-伊红（HE）染色、尼氏染色和TUNEL检测的组织学分析表明，电针减少了大脑皮层和海马体中的神经元损伤、细胞凋亡和髓鞘损失。此外，电针治疗显著降低了脑组织中促炎细胞因子肿瘤坏死因子-α（TNF-α）的表达，表明其具有抗炎作用。免疫荧光和蛋白质印迹分析显示，电针抑制了CH模型中小胶质细胞和星形胶质细胞的过度激活。具体而言，电针分别抑制了小胶质细胞和星形胶质细胞激活标志物离子钙结合衔接分子1（Iba1）和胶质纤维酸性蛋白（GFAP）的表达。此外，电针通过下调诱导型一氧化氮合酶（iNOS）并上调精氨酸酶1（Arg1）促进小胶质细胞向M2抗炎表型极化。同样，电针降低了A1星形胶质细胞标志物C3的表达，从而防止星形胶质细胞向促炎状态极化。经历氧糖剥夺（OGD）的脑片培养证实，类似于电针的电刺激在缺氧条件下抑制了小胶质细胞和星形胶质细胞的激活。总之，电针通过减轻神经炎症、抑制胶质细胞过度激活和促进抗炎表型来改善CH诱导小鼠的认知功能。这些发现突出了电针作为慢性缺氧相关认知障碍治疗干预手段的潜力。
