中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (7): 1153-1158.doi: 10.4103/1673-5374.187056

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

染料木素防止海马神经元丢失抑制其线粒体凋亡的途径

  

  • 出版日期:2016-07-30 发布日期:2016-07-30
  • 基金资助:
    国家自然科学基金资助项目（81202941）；海外访问和研究的优秀中青年教师在安徽省高校重点项目（gxfxzd2016119）；安徽省高校自然科学研究重点项目（kj2016a406）

Genistein suppresses the mitochondrial apoptotic pathway in hippocampal neurons in rats with Alzheimer’s disease

Yan Wang1, 2, Biao Cai1, 2, *, Jing Shao1, 2, Ting-ting Wang1, 2, Run-ze Cai1, Chang-ju Ma1, Tao Han1, Jun Du1   

  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
  • Online:2016-07-30 Published:2016-07-30
  • Contact: Biao Cai, caibiao9035@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81202941; 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.

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摘要：

染料木素具有对抗β淀粉样蛋白的毒性，但其作用机制还不是很明确。我们假设染料木素可以通过抑制线粒体凋亡途径起到保护神经元的作用，从而起到防治阿尔茨海默病的作用。实验给予大鼠10，30，90 mg/kg染料木素连续灌胃7 d后，以腹腔注射D-半乳糖联合脑内注射β淀粉样蛋白25-35诱导制备阿尔茨海默病大鼠模型，继续给药42 d， TUNEL染色显示海马CA1区神经元凋亡减少，Western blot检测显示线粒体凋亡途径中关键物质细胞色素C、Bax和Caspase-3蛋白表达下调，免疫组织化学染色显示细胞色素C、Bax免疫反应下降，Morris水迷宫实验也发现阿尔茨海默病大鼠的逃避潜伏期明显缩短。说明染料木素可防止海马神经元丢失，改善阿尔茨海默病所致的学习记忆功能损害，其作用机制与下调细胞色素C、Bax和Caspase-3蛋白表达有关。 

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

关键词: 神经再生, 神经推行性病, 染料木素, 阿尔茨海默病, 线粒体, 细胞凋亡, 海马, Bax, 细胞色素C, Caspase-3, 学习, 记忆, 神经保护, 国家自然科学基金

Abstract: Genistein is effective against amyloid-β toxicity, but the underlying mechanisms are unclear. We hypothesized that genistein may protect neurons by inhibiting the mitochondrial apoptotic pathway, and thereby play a role in the prevention of Alzheimer’s disease. A rat model of Alzheimer’s disease was established by intraperitoneal injection of D-galactose and intracerebral injection of amyloid-β peptide (25–35). In the genistein treatment groups, a 7-day pretreatment with genistein (10, 30, 90 mg/kg) was given prior to establishing Alzheimer’s disease model, for 49 consecutive days. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated a reduction in apoptosis in the hippocampus of rats treated with genistein. Western blot analysis showed that expression levels of capase-3, Bax and cytochrome c were decreased compared with the model group. Furthermore, immunohistochemical staining revealed reductions in cytochrome c and Bax immunoreactivity in these rats. Morris water maze revealed a substantial shortening of escape latency by genistein in Alzheimer’s disease rats. These findings suggest that genistein decreases neuronal loss in the hippocampus, and improves learning and memory ability. The neuroprotective effects of genistein are associated with the inhibition of the mitochondrial apoptotic pathway, as shown by its ability to reduce levels of caspase-3, Bax and cytochrome c.

Key words: nerve regeneration, genistein, Alzheimer’s disease, mitochondrion, apoptosis, hippocampus, Bax, cytochrome c, caspase-3, learning, memory, neural regeneration