酸枣仁汤对氯苯丙氨酸诱导失眠大鼠模型治疗机制的研究

doi:10.3976/j.issn.1002-4026.2021.06.005

Abstract

Abstract:

The therapeutic effects and mechanism of action of Suanzaoren decoction on p-chlorophenylalanine (PCPA)-induced insomnia in rats were investigated. We randomly divided 20 male and 20 female 8-week-old Sprague-Dawley rats into four groups of ten rats (five male and five female rats) each as follows: Suanzaoren decoction group, diazepam group, model group, and blank group. We established a rat model of insomnia by the intraperitoneal injection of PCPA suspension and evaluated the changes in the sleep behavior and mood of rats after an open-field experiment and an elevated plus-maze experiment. After two weeks of treatment, rat serum samples were collected to analyze the changes in the levels of monoamine neurotransmitters, amino acid neurotransmitters, and inflammatory factors. According to the results of the elevated plus-maze experiment, compared with the blank group, rats with PCPA-induced insomnia had a significant decrease in the percentage of open arm residence time (t_oc) and a decrease in the percentage of open arm entry time (N_oc), which indicated that the model was constructed successfully. Compared to the model group, the levels of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) in the Suanzaoren decoction group increased significantly, whereas the increase in norepinephrine (NE) level was not significant. In contrast, dopamine (DA) and glutamic acid (Glu) levels decreased significantly. Compared to the model group, pro-inflammatory cytokine interleukin (IL)-1β level was significantly decreased, and anti-inflammatory cytokine IL-10 level was significantly increased in Suanzaoren decoction group. Compared to the diazepam group, the decrease in DA level in Suanzaoren decoction group was more significant, whereas the level of tumor necrosis factor α (TNF-α) in diazepam group reduced more significantly than that in Suanzaoren group. However, the levels of 5-HT, GABA, NE, Glu, IL-1β, and IL-10 in these two groups showed similar trends with no statistically significant differences. The study suggested that Suanzaoren decoction relieved insomnia by increasing the levels of inhibitory neurotransmitters, reducing those of excitatory neurotransmitters, and restoring those of pro- and anti-inflammatory cytokines. This study will serve as a scientific basis for demonstrating the efficacy and validating the prescription of Suanzaoren decoction in treating insomnia.

Key words: Suanzaoren decoction, insomnia, rat model, open field experiment, elevated plus-maze experiment, neurotransmitter, inflammatory cytokines

CLC Number:

R285.5

LIU Hao, HAN Chang-sheng, CHI Xian-su, YANG Zhen-xiao, WANG Xiang-yu, WANG Xin, MA Ke. Therapeutic effects and mechanism of action of Suanzaoren decoction, a classical prescription, on p-chlorophenylalanine-induced insomnia in rats[J].Shandong Science, 2021, 34(6): 32-40.

Figures/Tables 7

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组别	总距离/cm	中央区进入次数/次	中央区时间/s
空白组	1 923.36±266.16	3.00±1.41	527.37±256.42
模型组	1 260.30±136.15^*	1.67±0.35^***	381.61±83.01^***

组别	开臂停留时间百分比(t_oc)	进入开臂次数百分比(N_oc)
空白组	0.076±0.038	0.119±0.018
模型组	0.056±0.012^***	0.106±0.024^*

组别	ρ(5-HT)/(ng·L^-1)	ρ(DA)/(pg·mL^-1)	ρ(NE)/(ng·L^-1)
空白组	325.02±58.42	65.77±6.76	101.47±11.54
模型组	243.85±52.72^*	74.34±8.55^*	145.79±20.19^*
地西泮组	270.74±11.79^※	81.88±3.90^※	157.71±22.18^※
酸枣仁汤组	330.68±44.60^※	61.31±3.82^※※	153.81±22.77^※※※

组别	c(Glu)/(μmol·L^-1)	c(GABA)/(μmol·L^-1)
空白组	10.13±1.55	1 879.46±215.85
模型组	12.55±1.05^*	1 302.80±318.80^**
地西泮组	7.63±1.17^※※	1 932.75±170.51^※※
酸枣仁汤组	9.31±1.81^※※	1 721.13±181.81^※※

组别	ρ(TNF-α)/(ng·L^-1)	ρ(IL-1β)/(ng·L^-1)	ρ(IL-10)/(ng·L^-1)
空白组	224.65±27.72	26.83±2.89	101.60±11.99
模型组	302.32±67.31^**	33.04±3.31^**	59.62±10.28^**
地西泮组	230.00±32.07^※※	26.15±5.59^※※	99.35±15.16^※※
酸枣仁汤组	316.72±30.41^※※※	24.67±2.32^※※	90.13±16.13^※※

Therapeutic effects and mechanism of action of Suanzaoren decoction, a classical prescription, on p-chlorophenylalanine-induced insomnia in rats

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