中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (9): 1561-1567.doi: 10.4103/1673-5374.237119

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

3'-大豆苷元磺酸钠能减轻慢性脑低灌注引起的海马损伤和记忆障碍

  

  • 收稿日期:2018-05-19 出版日期:2018-09-15 发布日期:2018-09-15
  • 基金资助:

    中国国家自然科学基金项目（81560583），江西省自然科学基金项目（20142BAB205021）

3′-Daidzein sulfonate sodium protects against memory impairment and hippocampal damage caused by chronic cerebral hypoperfusion

Xiao Li1, Rui-Zhen Liu1, Qi Zeng2, Zhi-Hua Huang1, Jian-Dong Zhang1, Zong-Liang Liu1, Jing Zeng1, Hai Xiao3   

  1. 1 Gannan Medical University, Ganzhou, Jiangxi Province, China
    2 Department of Ultrasound, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, China
    3 Department of Pathology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, China
  • Received:2018-05-19 Online:2018-09-15 Published:2018-09-15
  • Contact: Jing Zeng or Hai Xiao,zengjing61@hotmail.com or 13576675898@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81560583; the Natural Science Foundation of Jiangxi Province of China, No. 20142BAB205021.

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摘要：

3'-大豆苷元磺酸钠是在中药葛根的主要活性成分大豆黄酮基础上新合成的一种水溶性化合物，具有神经调控作用。实验假设这种调控作用对海马损伤及记忆障碍有治疗效应。未验证刺激as，设计以双血管闭塞方法永久闭塞颈总动脉建立慢性脑低灌注大鼠模型，3周后给予0.1，0.2，0.4mg/kg 3'-大豆苷元磺酸钠灌胃，1次/d，持续5周。以Morris水迷宫观察记忆和学习障碍的变化，以TUNEL染色分析海马CA1，CA3和齿状回区域的细胞凋亡情况，以苏木精-伊红染色观察海马CA1，CA3和齿状回区域的神经元形态，以Western blot分析海马中PKA/ERK1/2/CREB信号通路中PKA、ERK1/2E和CREB的磷酸化情况。结果显示，经3'-大豆苷元磺酸钠治疗后，慢性脑低灌注大鼠的记忆和学习能力明显改善，海马CA1，CA3和齿状回区域神经元损伤和凋亡明显减轻，海马内PKA、ERK1/2E和CREB的磷酸化降低。提示3'-大豆苷元磺酸钠可能通过激活PKA/ERK1/2/CREB信号传导通路，改善慢性脑低灌注引起的记忆障碍和海马损伤。

orcid:0000-0002-1265-1180(Jing Zeng)
        0000-0003-1125-3196(Hai Xiao)

关键词: 记忆和学习障碍, 慢性脑低灌注, 3'-大豆苷元磺酸钠, PKA/ERK1/2/CREB信号通路, 神经保护, 海马, 神经再生

Abstract:

3′-Daidzein sulfonate sodium (DSS) is a new synthetic water-soluble compound derived from daidzein, a soya isoflavone that plays regulatory roles in neurobiology. In this study, we hypothesized that the regulatory role of DSS in neurobiology exhibits therapeutic effects on hippocampal damage and memory impairment. To validate this hypothesis, we established rat models of chronic cerebral hypoperfusion (CCH) by the permanent occlusion of the common carotid arteries using the two-vessel occlusion method. Three weeks after modeling,rat models were intragastrically administered 0.1, 0.2, and 0.4 mg/kg DSS, once a day, for 5 successive weeks. The Morris water maze test was performed to investigate CCH-induced learning and memory deficits. TUNEL assay was used to analyze apoptosis in the hippocampal CA1, CA3 regions and dentate gyrus. Hematoxylin-eosin staining was performed to observe the morphology of neurons in the hippocampal CA1, CA3 regions and dentate gyrus. Western blot analysis was performed to investigate the phosphorylation of PKA, ERK1/2 and CREB in the hippocampal PKA/ERK1/2/CREB signaling pathway. Results showed that DSS treatment greatly improved the learning and memory deficits of rats with CCH, reduced apoptosis of neurons in the hippocampal CA1, CA3 regions and dentate gyrus, and increased the phosphorylation of PKA, ERK1/2, and CREB in the hippocampus. These findings suggest that DSS protects against CCH-induced memory impairment and hippocampal damage possibly through activating the PKA/ERK1/2/CREB signaling pathway.

Key words: nerve regeneration, learning and memory deficits, chronic cerebral hypoperfusion, 3′-daidzein sulfonate sodium, PKA/ERK1/2/CREB signaling pathway, neuroprotection, hippocampus, neural regeneration