中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (9): 1479-1484.doi: 10.4103/1673-5374.215260

• 原著:退行性病与再生 • 上一篇    下一篇

染料木素调节阿尔茨海默病大鼠CaMKIV蛋白的表达保护损伤海马神经元

  

  • 收稿日期:2017-08-20 出版日期:2017-09-15 发布日期:2017-09-15
  • 基金资助:

    国家自然科学基金（81202941，81574040）；安徽省海外访问和研究的优秀中青年教师关键项目（gxfxzd2016119）；安徽省自然科学基金（kj2016a406）；安徽省高校优秀青年教师支持基础项目（gxyq zd2016138）

Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase IV protein levels in Alzheimer’s disease model rats

Shu Ye1, Ting-ting Wang1, Biao Cai1, 2, Yan Wang1, 2, Jing Li1, 2, Ji-xian Zhan1, Guo-ming Shen1, 2   

  1. 1 School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China
    2 Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui Province, China
  • Received:2017-08-20 Online:2017-09-15 Published:2017-09-15
  • Contact: Biao Cai, caibiao9035@163.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81202941 and 81574040; the Key Project Foundation of Oversea Visiting and Research for the Excellent Young and Middle-aged Faculties in Universities of Anhui Province in China, No.gxfxZD2016119; the Key Project Foundation of Natural Science Research in Universities of Anhui Province in China, No. KJ2016A406; the Key Project Foundation of Support Program for the Excellent Young Faculties in Universities of Anhui Province in China, No. gxyq ZD2016138.

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摘要：

染料木素对阿尔茨海默病具有神经保护作用，但其作用机制仍需进一步明确。越来越多的证据表明tau蛋白过度磷酸化引起的神经纤维缠结是阿尔茨海默病的主要病理改变之一，而钙调蛋白依赖性蛋白激酶IV(CaMKIV)可以引起tau蛋白的磷酸化。实验假设染料木素通过调节阿尔茨海默病大鼠CaMKIV蛋白的表达缓解tau蛋白的过度磷酸化给予大鼠预先灌胃染料木素(90 mg/kg)7 d后，腹腔注射D-半乳糖联合脑内注射Aβ25-35建立阿尔茨海默大鼠模型，建模后继续灌胃染料木素(90 mg/kg)42 d，并以Morris水迷宫测试、Western blot检测及苏木精-伊红染色检测发现，染料木素可明显降低阿尔茨海默病大鼠的逃避潜伏期和海马p-tau，CaM，CaMKK，p-CaMKIV蛋白表达，减轻海马神经元损伤，增加阿尔茨海默大鼠穿越原平台位置的次数。说明染料木素可调节CaMKIV蛋白表达，抑制tau蛋白的过度磷酸化，从而发挥对阿尔茨海默的神经保护作用。

orcid:0000-0002-3375-0073(Biao Cai)

关键词: 神经再生, 神经退行性变, 染料木素, 阿尔茨海默病, 神经保护, 海马, 学习, 记忆, tau蛋白, CaMKIV, CaM, CaMKK

Abstract:

Genistein has a neuroprotective effect in Alzheimer’s disease, but its mechanism of action needs further clarification. Accumulating evidence suggests that excessive phosphorylation of tau protein causes production of neurofibrillary tangles, which is one of the main pathological characteristics of Alzheimer’s disease, and tau protein can be phosphorylated by calcium/calmodulin dependent protein kinase IV (CAMK4). After 7 days of pre-administration of genistein (90 mg/kg), an Alzheimer’s disease rat model was established using an intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-β peptide (25–35). The rat was then continuously administered genistein (90 mg/kg) for 42 days. The Morris water maze test, western blotting and hematoxylin-eosin staining results showed that genistein significantly decreased the escape latency and increased the number of times crossing the platform, reduced p-tau,CALM, CAMKK1 and p-CAMK4 protein levels in the hippocampus, and alleviated hippocampal neuron damage. These findings indicate that genistein may play a neuroprotective role in Alzheimer’s disease through regulating CAMK4 to modulate tau hyperphosphorylation.

Key words: nerve regeneration, neurodegeneration, genistein, Alzheimer’s disease, neuroprotection, hippocampus, learning, memory, tau protein, CAMK4, CALM, CAMKK1, neural regeneration