防己地黄汤通过神经递质及炎性因子调节改善失眠的作用机制研究

Mechanism of Fangji Dihuang Decoction in Improving Insomnia by Regulating Neurotransmitters and Inflammatory Factors

目的旨在通过动物实验方法探讨防己地黄汤治疗失眠的作用机制。方法通过氯苯丙氨酸诱导失眠建立失眠小鼠模型,运用ELISA法检测小鼠下丘脑组织中的5-羟色胺(5-HT)、γ-氨基丁酸(GABA)、去甲肾上腺素(NE)、多巴胺(DA)水平以及血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平。结果与空白组相比,模型组小鼠入睡潜伏期延长且睡眠时间减少(P<0.05);与模型组比较,防己地黄汤高剂量组小鼠入睡潜伏期明显缩短,且总睡眠时间延长,差异有统计学意义(P<0.05);防己地黄汤中剂量组及阳性对照组小鼠入睡潜伏期均缩短,差异有统计学意义(P<0.05)。与空白组比较,模型组未移动累计持续时间缩短、站立次数减少、粪便粒数减少及水中静止时间增加,差异有统计学意义(P<0.05);而防己地黄汤高剂量组未移动累计持续时间、站立次数和粪便粒数增加,水中静止时间减少,差异有统计学意义(P<0.05)。神经递质水平分析显示,模型组小鼠下丘脑中5-HT、GABA较空白组明显降低,NE和DA含量较空白组明显升高(P<0.05);与模型组比较,防己地黄汤中、高剂量组及阳性对照组5-HT、GABA均明显上升,NE和DA明显降低,差异有统计学意义(P<0.05)。炎症因子分析表明,模型组小鼠IL-1β和TNF-α水平较空白组升高,防己地黄汤中、高剂量组及阳性对照组IL-1β和TNF-α水平较模型组降低,差异有统计学意义(P<0.05)。结论防己地黄汤作为一种具有多靶点作用的复方中药,通过调节神经递质和炎性因子平衡,其在神经递质5-HT、GABA提升和TNF-α降低方面的效果明显,为治疗失眠的应用方案提供了实验支持。

Objective This study aims to explore the mechanism of Fangji Dihuang Decoction(FDD)in the treatment of insomnia through animal experiments.Methods A mouse model of insomnia was established by inducing insomnia with chlorphenylalanine.The levels of 5-hydroxytryptamine(5-HT),gamma-aminobutyric acid(GABA),norepinephrine(NE)and dopamine(DA)in the hypothalamic tissue of mice,and the serum levels of tumor necrosis factorα(TNF-α)and interleukin-1β(IL-1β)were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the blank group,the model group showed prolonged sleep latency and reduced sleep time(P<0.05).Compared with the model group,the high-dose FDD group exhibited shortened sleep latency and prolonged total sleep time(P<0.05),and the middle dose FDD group and the positive control group also showed shortened sleep latency(P<0.05).Compared with the blank group,the model group showed shortened cumulative duration of non-movement,reduced times of standing,decreased number of fecal particles,and increased time of resting in water(P<0.05),while the high-dose FDD group exhibited increased cumulative duration of non-movement,times of standing and number of fecal particles,and decreased time of resting in water(P<0.05).The analysis of neurotransmitter levels in the hypothalamus showed that 5-HT and GABA were decreased,while NE and DA were increased in the model group compared with those in the blank group;and 5-HT and GABA were increased,while NE and DA were decreased in the middle and high dose FDD groups and the positive control group compared with those in the model group(P<0.05).The analysis of inflammatory factors showed that the IL-1βand TNF-αlevels in the model group were higher than those in the blank group,and the two indicators in the middle and high dose FDD groups and the positive control group were lower than those in the model group(P<0.05).Conclusion Fangji Dihuang Decoction,as a multi-target traditional Chinese medicine compound,is effective in regulating the balance of neurotransmitters and inflammatory factors by increasing neurotransmitters 5-HT and GABA,and decreasing TNF-α,which provides experimental support for the treatment of insomnia.