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芦丁改善经前烦躁障碍肝气郁证抑郁症状的机制研究
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| 篇名： | 芦丁改善经前烦躁障碍肝气郁证抑郁症状的机制研究 |
| TITLE： | Study on the mechanism of rutin in ameliorating depressive symptoms associated with premenstrual dysphoric disorder characterized by liver qi stagnation syndrome |
| 摘要： | 目的 探索芦丁改善经前烦躁障碍（PMDD）肝气郁证抑郁症状的作用机制。方法采用网络药理学方法挖掘PMDD和芦丁作用的交集靶点，构建蛋白-蛋白相互作用网络以筛选核心靶点，并进行基因本体、京都基因和基因组数据库通路富集分析。利用分子对接技术验证核心靶点和芦丁的结合能力。摘取雌性Wistar大鼠双侧卵巢并进行人工激素诱导后，将其随机分为正常组（10只）和造模组（50只）。取造模组大鼠，以择时束缚应激法构建PMDD肝气郁证模型。将造模成功的大鼠分为模型组、氟西汀组（阳性对照）、芦丁组，每组12只。于每天上午9：00灌胃相应药液或水，持续2个动情周期。利用旷场实验、强迫游泳实验和Y迷宫实验评价芦丁对模型大鼠行为学指标的影响，观察其脑海马组织神经元树突棘密度，检测其血清脑源性神经营养因子（BDNF）水平以及脑海马组织中BDNF、酪氨酸激酶受体B（TrkB）、突触核蛋白（Syn）、突触后密度蛋白95（PSD95）的表达情况。结果网络药理学和分子对接结果显示，芦丁改善PMDD肝气郁证的核心靶点包括BDNF、TrkB、PSD65、Syn等。实验验证结果显示，芦丁可显著增加非接受期PMDD肝气郁证模型大鼠的自发轮流行为得分，缩短悬浮不动时间，提高脑海马组织中神经元树突棘密度，上调血清BDNF水平和脑海马组织中BDNF、TrkB、Syn蛋白的表达（P＜0.05）；但对接受期模型大鼠上述指标无显著影响（P＞0.05）。结论芦丁可缓解PMDD肝气郁证模型大鼠的抑郁症状，增强其空间记忆能力，减少神经元损伤；上述作用可能与该成分激活BDNF/TrkB信号通路、上调Syn蛋白的表达有关。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanisms of rutin in alleviating depressive symptoms associated with premenstrual dysphoric disorder （PMDD） characterized by liver qi stagnation syndrome. METHODS Network pharmacology was employed to identify the intersecting targets of action between PMDD and rutin. A protein-protein interaction network was constructed to screen core targets， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Molecular docking simulations validated rutin’s binding affinity to core targets. The bilateral ovaries of female Wistar rats were removed， followed by artificial hormone induction. The rats were then randomly divided into normal group （10 rats） and modeling group （50 rats）. PMDD rat model with liver qi stagnation syndrome was established via restraint stress. The successfully modeled rats were further divided into model group， fluoxetine group （positive control） and rutin group， with 12 rats in each group. The corresponding drug solutions or water were administered by gavage at 9：00 a.m. every day， continuing for two estrous cycles. The open-field test， forced swimming test and Y-maze test were utilized to evaluate the effects of rutin on the behavioral indexes of model rats. Additionally， the density of neuronal dendritic spines in the hippocampal tissues of the rats was observed. Serum brain-derived neurotrophic factor （BDNF） levels and the expressions of BDNF， tyrosine kinase receptor type B （TrkB）， synuclein （Syn）， and postsynaptic density protein 95 （PSD95） in hippocampal tissues were quantified， respectively. RESULTS Network pharmacology and molecular docking revealed the core targets through which rutin ameliorated PMDD characterized by liver qi stagnation syndrome included BDNF， TrkB， PSD65， Syn， etc. The results of experimental validation demonstrated that rutin significantly increased the spontaneous alternation behavior scores of PMDD model rats with liver qi stagnation syndrome during the non-receptive phase， shortened their immobility time during the forced swimming test， and enhanced the density of neuronal dendritic spines in the hippocampal tissues. Additionally， rutin upregulated the levels of serum BDNF and the protein expressions of BDNF， TrkB and Syn in the hippocampal tissues （P＜0.05）. However， it had no significant effect on the above indexes in model rats during the receptive phase （P＞0.05）. CONCLUSIONS Rutin ameliorates depressive symptoms， enhances spatial memory capabilities， and reduces neuronal damage in PMDD model rats with liver qi stagnation syndrome. These effects may be associated with the activation of BDNF/TrkB signaling pathway and upregulation of Syn protein expression. |
| 期刊： | 2025年第36卷第12期 |
| 作者： | 张艺伟；宋现良；任亚爽；郭德第；宋润蔚；陈玺泰；赵怀伟；宋春红 |
| AUTHORS： | ZHANG Yiwei， SONG Xianliang，REN Yashuang，GUO Dedi，SONG Runwei，CHEN Xitai，ZHAO Huaiwei，SONG Chunhong |
| 关键字： | 芦丁；经前烦躁障碍；肝气郁证；脑源性神经营养因子；神经元损伤 |
| KEYWORDS： | rutin； premenstrual dysphoric disorder； liver qi stagnation syndrome； brain-derived neurotrophic factor； neuronal |
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