生物学杂志

生物学杂志 ›› 2025, Vol. 42 ›› Issue (6): 62-.doi: 10.3969/j.issn.2095-1736.2025.06.062

• 研究报告 • 上一篇    下一篇

多花黄精多糖对抑郁模型小鼠内侧前额叶皮层Netrin-1/DCC表达的影响

秦抗洪1， 程　平2， 王　斌2， 朱国旗2， 杨绍杰3   

  1. 1. 皖西卫生职业学院， 六安 237000； 2. 安徽中医药大学 分子生物学（脑病）
    重点实验室， 合肥 230012； 3. 安徽中医药大学第二附属医院， 合肥 230012
  • 出版日期:2025-12-18 发布日期:2025-12-19
  • 通讯作者: 朱国旗，博士，研究员，研究方向为神经生物学，E-mail:Guoqizhu@gmail.com；杨绍杰，博士，助理研究员，研究方向为神经药理学，E-mail:1558589910@qq.com；朱国旗和杨绍杰为共同通信作者
  • 作者简介:秦抗洪，硕士，副教授，研究方向为神经病学与脑血管疾病，E-mail:2357577405@qq.com
  • 基金资助:
    国家自然科学基金项目（82404890）； 安徽省高等学校省级质量工程一流核心课程研究项目（2023hxkc061）； 安徽省高等学校省级质量工程教学研究项目（2020jyxm2122）； 安徽省高等学校省级教学示范课项目（2020SJJXSFK2478）； 安徽高校人文社会科学重点研究项目（SK2020A0719）

Effect of Polygonatum sibiricum polysaccharides on expression of Netrin-1/DCC in medial prefrontal cortex of depressed mice

QIN Kanghong1, CHENG Ping2, WANG Bin2, ZHU Guoqi2, YANG Shaojie 3   

  1. 1. West Anhui Health Vocational College, Lu’an 237000, China;
    2. Key Laboratory of Molecular Biology (Brain Diseases), Anhui University of Chinese Medicine, Hefei 230012, China;
    3. The Second Affiliation Hospital of Anhui University of Chinese Medicine, Hefei 230012, China
  • Online:2025-12-18 Published:2025-12-19

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摘要： 研究旨在从内侧前额叶皮层（medial prefrontal cortex，mPFC）Netrin-1/DCC探讨多花黄精多糖（Polygonatum sibiricumpolysaccharides，PSP）干预抑郁样行为的机制。建立习得性无助（learned helplessness, LH）和慢性不可预温和应激（chronic unpredictable mild stress，CUMS）抑郁模型后，连续14 d给予PSP（400 mg/kg），采用旷场、悬尾及强迫游泳实验评价小鼠的抑郁样行为；免疫印迹检测小鼠内侧前额叶皮层中Netrin-1/DCC信号通路以及GFAP、NF-κB、IL-1β、GluN2A、GluN2B和PSD95的表达水平。结果发现：与对照小鼠相比，模型小鼠在悬尾及强迫游泳实验中静止时间增加，PSP给药可以改善模型小鼠的抑郁样行为；同时，模型小鼠mPFC中Netrin-1/DCC，与炎症反应相关的GFAP、NF-κB、IL-1β以及与突触相关的GluN2A、GluN2B的表达水平升高，PSD95的表达水平降低。而PSP可以抑制Netrin-1/DCC的激活，下调GFAP、NF-κB、IL-1β、GluN2A及GluN2B的表达水平，上调PSD95的表达水平。研究表明，抑郁发生时Netrin-1/DCC信号通路激活，而PSP可能通过抑制Netrin-1/DCC激活进而调节突触功能和炎症反应，这可能是PSP发挥改善抑郁作用的重要机制。

关键词: 抑郁, 结肠癌缺失基因, 多花黄精多糖, 突触损伤, 炎症反应

Abstract: This study aimed to investigate the mechanism by whichPolygonatum sibiricumpolysaccharides (PSP) modulate depression-like behaviors via the Netrin-1/DCC pathway in the medial prefrontal cortex (mPFC). After establishing the learned helplessness (LH) and chronic unpredictable mild stress (CUMS) depression models, PSP (400 mg/kg) was administered continuously for 14 days. The depressive-like behaviors of the mice were evaluated using the open field test, tail suspension test, and forced swimming test. Western blot analysis was performed to detect the Netrin-1/DCC signaling pathway in the medial prefrontal cortex of mice, as well as the expression levels of GFAP, NF-κB, IL-1β, GluN2A, GluN2B, and PSD95. The results indicated that, compared to the control group, the model group of mice exhibited increased immobility time in both the tail suspension and forced swimming tests. Administration of PSP reduced depression-like behaviors in model mice. Concurrently, in the mPFC of the model group mice, the expression levels of Netrin-1/DCC, GFAP, NF-κB, and IL-1β, which were associated with inflammatory responses, as well as GluN2A and GluN2B related to synaptic function, were elevated, while the expression level of PSD95 was reduced. PSP was found to inhibit the activation of Netrin-1/DCC, downregulate GFAP, NF-κB, IL-1β, GluN2A, and GluN2B, and upregulate PSD95 expression. The study indicated that the Netrin-1/DCC signaling pathway was abnormally activated during the onset of depression, and that PSP might exert its antidepressant effects by inhibiting this pathway, thereby regulating synaptic function and inflammatory responses. This process might be a crucial mechanism through which PSP improves depressive symptoms.

Key words: depression, DCC;Polygonatum sibiricumpolysaccharides, synaptic injury, inflammatory response

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