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黑果枸杞改善睡眠的作用及机制研究
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| 篇名： | 黑果枸杞改善睡眠的作用及机制研究 |
| TITLE： | Study on the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep |
| 摘要： | 目的 探究黑果枸杞改善睡眠的作用及机制。方法借助网络药理学挖掘黑果枸杞改善睡眠的活性成分及对应疾病靶点，并进行富集分析。以咖啡因诱导斑马鱼构建睡眠剥夺模型，分别给予0.1、0.2、0.4mg/mL黑果枸杞提取物（LRME）干预24h后，观察斑马鱼行为学变化和脑部神经元病理学变化，检测斑马鱼体内炎症因子[白细胞介素6（IL-6）、IL-1β、IL-10、肿瘤坏死因子α（TNF-α）]、氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）]和神经递质[5-羟色胺（5-HT）、γ-氨基丁酸（GABA）、谷氨酸（Glu）、多巴胺（DA）和去甲肾上腺素（NE）]水平，并检测斑马鱼体内蛋白激酶B1（AKT1）、磷酸化AKT1（p-AKT1）、表皮生长因子受体（EGFR）、B细胞淋巴瘤2（Bcl-2）、肉瘤原癌基因编码的非受体酪氨酸激酶（SRC）、热休克蛋白90α家族A类成员1（HSP90AA1）蛋白表达水平。结果通过网络药理学挖掘共得到12个活性成分及176个疾病交集靶点，其中芹菜素、柚皮素等为核心活性成分，AKT1、EGFR等为核心靶点，EGFR酪氨酸激酶抑制剂耐药信号通路为关键通路。LRME低、中、高剂量组斑马鱼的睡眠改善率分别为54.60%、69.03%、77.97%，运动距离抑制比分别为0.57、0.83、0.95。与模型组比较，LRME中、高剂量组斑马鱼的静息次数、静息时间和静息距离均显著增加/延长（P＜0.05）；脑部神经元损伤减轻；体内IL-6、IL-1β、TNF-α、MDA、Glu、DA、NE水平和AKT1、p-AKT1、EGFR、SRC、HSP90AA1蛋白表达水平均显著降低（P＜0.05），IL-10、SOD、GSH-Px、CAT、5-HT、GABA水平和Bcl-2蛋白表达水平均显著升高（P＜0.05）。结论黑果枸杞具有改善睡眠的作用，其机制可能与调节炎症反应、氧化应激、神经递质平衡以及EGFR酪氨酸激酶抑制剂耐药信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway. |
| 期刊： | 2026年第37卷第01期 |
| 作者： | 谯明；赵耀；朱毅；曹叶霞；文丽梅；巩月红；李想；汪娟成；王涛；杨建华；胡君萍 |
| AUTHORS： | QIAO Ming，ZHAO Yao，ZHU Yi， CAO Yexia，WEN Limei，GONG Yuehong，LI Xiang，WANG Juanchen，WANG Tao，YANG Jianhua，HU Junping |
| 关键字： | 黑果枸杞；改善睡眠；失眠；网络药理学；斑马鱼 |
| KEYWORDS： | Lycium ruthenicum Murr.； improving sleep； insomnia； network pharmacology； zebrafish |
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