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秫米提取物对失眠小鼠睡眠的改善作用及机制研究
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王 娟 1, 2* ,吕辰子 ,赵彩蓉 ,赵泓瑜 ,李子昂 ,韩 香 ,孟祥龙 ,张朔生 (1.山西中医药大学中药
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与食品工程学院,山西 晋中 030619;2.山西中医药大学中药炮制山西省重点实验室,山西 晋中 030619;
3.东国大学韩医学院,韩国 庆州 38066)
中图分类号 R965;R285 文献标志码 A 文章编号 1001-0408(2024)03-0322-05
DOI 10.6039/j.issn.1001-0408.2024.03.10
摘 要 目的 研究秫米提取物对失眠小鼠的改善作用及可能机制。方法 将小鼠按随机数字表法分为空白组、模型组、阳性对照
组(地西泮,2.6 mg/kg)和秫米提取物低、中、高剂量组(1.2、2.4、4.8 g/kg),每组10只。除空白组外,其余各组小鼠均腹腔注射对氯
苯丙氨酸(PCPA)建立失眠模型。造模成功后,空白组和模型组小鼠灌胃等体积生理盐水,各给药组小鼠灌胃相应药物,灌胃体积
为0.01 mL/g,每天1次,连续7 d。给药结束后,进行旷场实验观察小鼠行为学变化,测定小鼠海马组织中5-羟色胺(5-HT)、5-羟吲
哚乙酸(5-HTAA)以及血清中5-HT、脑源性神经营养因子(BDNF)、白细胞介素2(IL-2)、IL-6、B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X
蛋白(Bax)含量;测定小鼠海马中磷脂酰肌醇 3 激酶/蛋白激酶 B/核因子 κB(PI3K/Akt/NF-κB)信号通路相关蛋白的表达水平。
结果 与模型组比较,秫米提取物高剂量组小鼠的总运动时间均显著延长、总静止时间均显著缩短(P<0.01),站立次数及修饰次
数均显著减少(P<0.01);血清中5-HT、BDNF、Bcl-2的含量和Bcl-2/Bax比值均显著升高,IL-2、IL-6、Bax的含量均显著降低(P<
0.05或P<0.01);海马组织中5-HTAA的含量及PI3K、Akt蛋白磷酸化水平均显著升高,NF-κB p65蛋白磷酸化水平显著降低(P<
0.05)。结论 高剂量秫米提取物对失眠小鼠有较好的改善效果,其作用机制可能与调控PI3K/Akt/NF-κB信号通路有关。
关键词 秫米;失眠;神经炎症;磷脂酰肌醇3激酶/蛋白激酶B/核因子κB信号通路
Effects and mechanism of Setaria italica extract on improving sleep in insomnia mice
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WANG Juan ,LYU Chenzi ,ZHAO Cairong ,ZHAO Hongyu ,LI Zi’ang ,HAN Xiang ,MENG
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Xianglong ,ZHANG Shuosheng (1. College of Traditional Chinese Medicine and Food Engineering, Shanxi
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University of Chinese Medicine, Shanxi Jinzhong 030619, China;2. Shanxi Provincial Key Laboratory of
Chinese Medicine Processing, Shanxi University of Chinese Medicine, Shanxi Jinzhong 030619, China;
3. College of Korean Medicine, Dongguk University, Gyeongju 38066, Korea)
ABSTRACT OBJECTIVE To investigate the effects of Setaria italica extract on improving insomnia model mice and to explore
its potential mechanisms. METHODS The mice were randomly assigned into blank group, model group, positive control group
(diazepam, 2.6 mg/kg), and S. italica extract low-dose, medium-dose and high-dose groups (1.2, 2.4, 4.8 g/kg), with 10 mice in
each group. Except for the blank group, all other groups received intraperitoneal injection of para-chlorophenylalanine (PCPA) to
establish the insomnia model. After modeling, the blank group and model group were given a constant volume of normal saline
intragastrically, and administration groups were given relevant medicine intragastrically, with a volume of 0.01 mL/g, once a day,
for 7 consecutive days. After the administration, the open-field test was conducted to observe the praxiological changes of mice,
and to determine the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HTAA) in the hippocampal tissue,
as well as the contents of 5-HT, brain-derived neurotrophic factor (BDNF), interleukin-2 (IL-2), IL-6, B-cell lymphoma-2 (Bcl-
2), and Bcl-2-associated X protein (Bax) in the serum. The expression of phosphoinositide 3-kinase/protein kinase B/nuclear factor-
κB (PI3K/Akt/NF-κB) signaling pathway related protein was determined in the hippocampus of mice. RESULTS Compared with
the model group, the total exercise time of mice in S. italica extract high-dose group was significantly prolonged, but the total rest
time was significantly shortened (P<0.01); the number of standing times and modification times were significantly reduced (P<
0.01). The contents of 5-HT, BDNF, and Bcl-2 in serum, and Bcl-2/Bax were significantly increased, while the contents of IL-2,
IL-6, and Bax were significantly reduced (P<0.05 or P<
Δ 基金项目 中 药 炮 制 山 西 省 重 点 实 验 室 项 目(No. 0.01). The content of 5-HTAA in the hippocampal tissue and
202104010910029);2022 年 山 西 省 中 药 材 产 业 体 系 项 目(No. the phosphorylation levels of PI3K and Akt proteins were
20220518) increased significantly, while the phosphorylation level of NF-
*第一作者 硕士研究生。研究方向:中药新产品开发与应用。 κB p65 protein was decreased significantly (P<0.05).
E-mail:wj978123@163.com
# 通信作者 教授,博士生导师。研究方向:中药炮制现代研究。 CONCLUSIONS High-dose of S. italica extract demonstrates
电话:0351-3179909。E-mail:zhangshuosheng@aliyun.com significant therapeutic effects on insomnia in mice, and the
· 322 · China Pharmacy 2024 Vol. 35 No. 3 中国药房 2024年第35卷第3期