中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 183-188.doi: 10.4103/1673-5374.344840

• 原著:退行性病与再生 • 上一篇    下一篇

淫羊藿苷干预可改善APP/PS1/Tau三转基因模式小鼠大脑的葡萄糖代谢

  

  • 出版日期:2023-01-15 发布日期:2022-06-17
  • 基金资助:
    国家自然科学基金项目(82060727,81660599);国家大学生创新训练项目(201910661009);遵义市科技局与遵义医科大学科技合作项目((2019)47)

Icariin ameliorates memory deficits through regulating brain insulin signaling and glucose transporters in 3×Tg-AD mice

Fei Yan1, Ju Liu1, Mei-Xiang Chen1, Ying Zhang1, Sheng-Jiao Wei1, Hai Jin2, Jing Nie1, Xiao-Long Fu1, Jing-Shan Shi1, Shao-Yu Zhou1, *, Feng Jin1, *   

  1. 1Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou Province, China; 2Institute of Digestive Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Shao-Yu Zhou, PhD, szhou@zmu.edu.cn; Feng Jin, PhD, jinfeng1115@zmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82060727 (to FJ), 81660599 (to FJ); the National Innovation Training Project for College Students, No. 201910661009 (to FJ); and the Science and Technology Cooperation Project of Zunyi Science and Technology Bureau and Zunyi Medical University, No. (2019) 47 (to XLF).

摘要:

淫羊藿苷是一种从中药淫羊藿中分离出来的异戊烯化黄酮类化合物,已被证明在阿尔茨海默病的实验模型中发挥神经保护作用。实验以最能模拟阿尔茨海默病的APP/PS1/Tau三转基因模式小鼠为研究对象,进一步探索淫羊藿苷的神经保护机制。研究发现在以淫羊藿苷60 mg/kg连续灌胃5个月后,转基因模型小鼠的记忆障碍明显改善,同时其大脑皮质中神经元和突触损伤明显减轻,淀粉样蛋白β积累和tau过度磷酸化也显著减少,同时胰岛素信号通路相关蛋白胰岛素受体、胰岛素受体底物 1、磷脂酰肌醇-3-激酶、AKT和糖原合酶激酶3β及其磷酸化水平的异常得到逆转,且脑葡萄糖转运体1和3的表达明显增加。上述结果提示淫羊藿苷可通过影响脑胰岛素信号传导和葡萄糖代谢改善阿尔茨海默病的学习记忆功能障碍。

https://orcid.org/0000-0002-1923-2093 (Fei Yan); https://orcid.org/0000-0002-8649-7462 (Shao-Yu Zhou); https://orcid.org/000-0002-2885-8733 (Feng Jin)

关键词: 阿尔茨海默病, 神经退行性疾病, 记忆, APP/PS1/Tau三转基因模式小鼠, 葡萄糖摄取, 淫羊藿苷, 脑胰岛素信号传导, 葡萄糖转运蛋白, tau过度磷酸化, 淀粉样蛋白β

Abstract: Icariin, a major prenylated flavonoid found in Epimedium spp., is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease. In this study, we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease. We performed behavioral tests, pathological examination, and western blot assay, and found that memory deficits of the model mice were obviously improved, neuronal and synaptic damage in the cerebral cortex was substantially mitigated, and amyloid-β accumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day. Furthermore, deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed, including the insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3-kinase, protein kinase B, and glycogen synthase kinase 3β, and the levels of glucose transporter 1 and 3 were markedly increased. These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters, which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.

Key words: Alzheimer’s disease, amyloid-beta, brain insulin signaling, glucose transporter, glucose uptake, icariin, memory, neurodegenerative disease, tau hyperphosphorylation, triple-transgenic Alzheimer’s disease mice