中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (5): 916-923.doi: 10.4103/1673-5374.297090

• 原著:退行性病与再生 • 上一篇    下一篇

电针可减轻D-半乳糖诱导的衰老大鼠认知缺陷

  

  • 出版日期:2021-05-15 发布日期:2020-12-29
  • 基金资助:

    国家自然科学基金项目(813737418147378681873380);世界国立针灸学会联合会Sun Guojie世界中医药针灸传承基地(201926号);深圳“魏以宗脊骨治疗队”项目(SZSM201612059

Preventive electroacupuncture reduces cognitive deficits in a rat model of D-galactose-induced aging

Chao-Chao Yu1, 2, #, Chuan He3, #, Yan-Jun Du3, Shan Gao4, Yuan-Fang Lin1, 2, Shu-Qin Wang1, 2, Li Wang3, Jia Wang4, Xue-Song Wang3, Tao Jiang3, Li-Hong Kong3, *#br#   

  1. 1 Department of Tuina, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, China;  2 The 4th Clinical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, China;  3 College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei Province, China;  4 Department of Acupuncture & Moxibustion, Wuhan Hospital of Integrated Chinese & Western Medicine, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, Hubei Province, China
  • Online:2021-05-15 Published:2020-12-29
  • Contact: Li-Hong Kong, MD, xiyu1618@sina.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81373741 (to LHK), 81473786 (to YJD), 81873380 (to YJD); Sun Guojie Inheritance Base for TCM Acupuncture-Moxibustion of World Federation of Acupuncture-Moxibustion Societies in Wuhan, China (World Federation of Acupuncture-Moxibustion Societies [2019] No. 26) (to YJD); and “Wei Yizong Chiropractic Team” Project Founded by Shenzhen of China, No. SZSM201612059 (to YFL).

摘要:

针刺可减轻阿尔茨海默病的认知功能障碍,但是电针能否预防或减轻衰老动物模型的认知障碍仍然不明确。有研究认为衰老过程中无序的表观遗传修饰可能在与年龄相关的认知能力下降中起重要作用。因而实验假设电针可能通过调节表观遗传修饰改善衰老过程中的认知功能。因此实验通过连续8周腹腔注射D-半乳糖120 mg/kg建立衰老大鼠模型,并从造模第1天起持续8周电针刺激白会和肾俞。结果显示,电针可减轻衰老大鼠的记忆障碍,并降低衰老起始脑区中缝背核中tau过度磷酸化和糖原合酶激酶蛋白和mRNA表达,同时也促进糖原合酶激酶启动子甲基化水平,且电针的作用效果强于针刺。而从第7周开始时,持续1周腹腔注射可影响表观遗传修饰的DNA甲基转移酶抑制剂5-氮杂2'-脱氧胞苷0.4 mg/kg,则能抑制电针的作用。结果表明,电针可能通过影响中缝背核中糖原合酶激酶的表观遗传修饰减轻衰老大鼠的认知障碍。实验于20171128日经湖北中医药大学动物伦理委员会批准,批准号HUCMS201712001

https://orcid.org/0000-0002-4287-0536 (Li-Hong Kong)

关键词: 中枢神经系统, 脑, 神经功能, 认知障碍, 电针, 阿尔茨海默病, DNA甲基化, 通路

Abstract: Acupuncture can reduce cognitive deficits in Alzheimer’s disease. However, whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood. Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline. Therefore, we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications. A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks. Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration. Preventive electroacupuncture alleviated memory impairment, decreased tau hyperphosphorylation, and reduced glycogen synthase kinase-3β protein and mRNA expression levels in the brainstem dorsal raphe nucleus, where intracellular neurofibrillary tangle lesions first occur. In addition, the DNA methylation level in the promoter region of the glycogen synthase kinase-3β gene was increased. The effects of preventive electroacupuncture were stronger than those of preventive acupuncture. Intraperitoneal injection of 0.4 mg/kg 5-aza-2ʹ-deoxycytidine, an inhibitor of DNA methyltransferase that blocks epigenetic modifications, antagonized the effects of preventive electroacupuncture. Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3β gene in the dorsal raphe nucleus. This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine, China (approval No. HUCMS201712001) on November 28, 2017.

Key words: Alzheimer’s disease, brain, central nervous system, cognitive impairment, DNA methylation, electroacupuncture, neurological function, pathways