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柴胡加龙骨牡蛎汤通过神经递质及食欲素改善失眠伴焦虑的作用机制研究 被引量:3

Study on the Mechanism of Action of Chaihu Jia Longgu Muli Decoction(柴胡加龙骨牡蛎汤)in Improving Insomnia with Anxiety through Neurotransmitters and Orexin
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摘要 目的观察柴胡加龙骨牡蛎汤对失眠伴焦虑小鼠的治疗作用并探讨其可能作用机制。方法选取50只SPF级雄性小鼠随机分为空白组、模型组、阳性对照组(氟西汀3.3 mg/kg)、中药低剂量组(柴胡加龙骨牡蛎汤5 g/kg)、中药高剂量组(柴胡加龙骨牡蛎汤10 g/kg),采用慢性不可预测轻度应激联合PCPA诱导建立失眠伴焦虑模型小鼠。造模成功后,空白组和模型组小鼠灌胃等体积0.9%氯化钠溶液,各给药组小鼠灌胃相应药物连续14 d,观察并记录各组小鼠的一般情况变化。给药结束后,通过旷场实验、糖水偏好实验、强迫游泳实验探究各组小鼠行为学差异;用酶联免疫吸附(ELISA)法检测小鼠脑组织食欲素A(orexin A,OXA)、γ-氨基丁酸(γ-aminobutyric acid,GABA)、5-羟色胺(5-hydroxy tryptamine,5-HT)、去甲肾上腺素(norepinephrine,NE)水平。结果与空白组比较,模型组小鼠糖水偏嗜率显著降低(P<0.05),水平活动次数、垂直站立次数显著减少(P<0.05),强迫游泳累计不动时间显著增加(P<0.05),血清中GABA、5-HT水平显著降低(P<0.05),血清中OXA、NE水平显著升高(P<0.05)。与模型组比较,阳性对照组与中药高剂量组小鼠糖水偏嗜率显著提高(P<0.05),水平活动次数、垂直站立次数显著增加(P<0.05),强迫游泳累计不动时间显著减少(P<0.05),血清中GABA、5-HT水平显著升高(P<0.05),血清中OXA、NE水平显著降低(P<0.05)。结论柴胡加龙骨牡蛎汤高剂量对失眠伴焦虑具有一定的治疗作用,其作用机制可能与增加血清中GABA、5-HT水平,降低NE水平,抑制血清中OXA表达有关。 Objective To investigate the therapeutic effects of Chaihu Jia Longgu Muli Decoction(柴胡加龙骨牡蛎汤)on insomnia with anxiety in mice and explore its potential mechanisms of action.Methods Using stratified randomization,SPF-grade male mice(n=50)were allocated into five groups:blank group,model group,positive control group(fluoxetine 3.3 mg/kg),low-dose Chinese herbal medicine group(Chaihu Jia Longgu Muli Decoction 5 g/kg),and high-dose Chinese herbal medicine group(Chaihu Jia Longgu Muli Decoction 10 g/kg).Adopting chronic unpredictable mild stress combined with PCPA induced to establish a model mouse with insomnia and anxiety.Following successful modeling,mice in the blank group and model group were gavaged with an equal volume of 0.9% sodium chloride solution,while mice in each medication administration group were gavaged with the appropriate medicines for 14 days,and the general changes of the mice in each group were observed and recorded.After drug administration,behavioral differences were investigated through open-field experiments,sugar-water preference,and forced-swimming experiments.The levels of orexin A(OXA),γ-aminobutyric acid(GABA),5-hydroxytryptamine(5-HT),and norepinephrine(NE)in mouse brain tissue were measured by enzyme-linked immunosorbent assay(ELISA)method.Results Compared with the blank group,the sugar water bias rate was significantly decreased(P<0.05),the number of horizontal activities and vertical standing were significantly decreased(P<0.05),the cumulative immobility time of forced swimming was significantly increased(P<0.05),the serum GABA and 5-HT contents were significantly decreased(P<0.05),and the serum OXA and NE contents were significantly increased(P<0.05).Compared with the model group,the prevalence of sugar water preference in the positive control group and the high-dose Chinese herbal medicine group was significantly increased(P<0.05),the number of horizontal activities and the number of vertical standing were significantly increased(P<0.05),the cumulative immobility time of forced swimming was significantly reduced(P<0.05),the serum GABA and 5-HT contents were significantly increased(P<0.05),and the serum OXA and NE contents were significantly decreased(P<0.05).Conclusion Chaihu Jia Longgu Muli Decoction high-dose has a therapeutic impact on insomnia with anxiety,and its mechanism of action may be connected to increasing the content of GABA and 5-HT in serum,decreasing the content of NE,and inhibiting the expression of OXA in serum.
作者 王瑜 陈昺伃 王彦华 WANG Yu;CHEN Bingyu;WANG Yanhua(The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,Henan,China;Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China)
出处 《辽宁中医药大学学报》 2025年第12期21-25,共5页 Journal of Liaoning University of Traditional Chinese Medicine
基金 国家自然科学基金青年科学基金项目(82305080) 河南省中医药科学研究专项课题(2023ZY2041)。
关键词 柴胡加龙骨牡蛎汤 失眠伴焦虑 食欲素A γ-氨基丁酸 5-羟色胺 去甲肾上腺素 Chaihu Jia Longgu Muli Decoction(柴胡加龙骨牡蛎汤) insomnia with anxiety OXA GABA 5-HT NE
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