苏格木勒-3汤水提物对小鼠镇静、催眠及失眠模型大鼠催眠的作用机制研究

Study on the Mechanism of Sedative and Hypnotic Effects of Water Extract of Sugmel-3 Decoction on Mice and Hypnotic Activity in Insomnia Model Rats

目的:研究苏格木勒-3汤水提物对小鼠镇静、催眠及对失眠模型大鼠催眠的作用机制。方法:将小鼠随机分为空白组(生理盐水,2 mL/100 g)、阳性对照组(阿普唑仑,0.15 mg/kg)和苏格木勒-3汤水提物高、低剂量组(90.0、45.0 mg/kg,以生药量计,下同),每组12只,各组小鼠每天灌胃给药1次,连续给药5 d,观察小鼠自主活动(活动时间和站立次数)变化及在戊巴比妥钠催眠剂量下(50 mg/kg)对小鼠入睡潜伏期和睡眠持续时间的影响。采用腹腔注射氯苯丙氨酸建立大鼠失眠模型,将成模大鼠随机分为模型组(生理盐水,2 mL/100 g)、阳性对照组(阿普唑仑,0.09 mg/kg)和苏格木勒-3汤水提物高、低剂量组(108.0、54.0 mg/kg),每组10只,并另取10只正常大鼠作为空白组(生理盐水,2 mL/100 g),各组大鼠每天灌胃给药1次,连续给药7 d后处死;采用酶联免疫吸附法检测各组大鼠脑组织内5-羟色胺(5-HT)、γ-氨基丁酸(GABA)、白细胞介素1β(IL-1β)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量。结果:在镇静、催眠实验中,与空白组比较,其余各组小鼠活动时间和站立次数均显著减少(P<0.05或P<0.01);苏格木勒-3汤水提物高剂量组和阳性对照组小鼠入睡潜伏期均显著缩短(P<0.05或P<0.01),苏格木勒-3汤水提物高剂量组小鼠睡眠持续时间显著延长(P<0.05)。在催眠作用机制实验中,与空白组比较,模型组大鼠脑组织内5-HT及GABA、SOD含量显著降低(P<0.05),IL-1β、MDA含量显著增加(P<0.05)。与模型组比较,阳性对照组和苏格木勒-3汤水提物高、低剂量组大鼠脑组织内5-HT含量显著增加(P<0.05或P<0.01);苏格木勒-3汤水提物高剂量组、阳性对照组大鼠脑组织内GABA、SOD含量显著增加(P<0.05或P<0.01),苏格木勒-3汤水提物高、低剂量组IL-1β含量显著降低(P<0.05),其余指标差异均无统计学意义(P>0.05)。结论:苏格木勒-3汤水提物具有较好的镇静、催眠作用,其催眠作用机制可能与中枢神经递质5-HT、GABA及细胞因子IL-1β水平有关。

OBJECTIVE：To study the hypnotic and sedative effects of water extract of Sugmel-3 decoction on mice and its effects on insomnia of insomnia model rats. METHODS：The mice were randomly divided into blank group （normal saline,2 mL/100 g）,positive control group（alprazolam,0.15 mg/kg）,water extract of Sugmel-3 decoction high-dose and low-dose groups （90.0,45.0 mg/kg,calculated by crude drug,similarly hereinafter）,with 12 mice in each group. Each group was given relevant medicine intragastrically once a day,for consecutive 5 days. The change of spontaneous activity（activity time and the number of standing）,the effects of hypnotic dose of pentobarbital sodium（50 mg/kg）on latency and duration of sleep were observed in mice. Insomnia rat model was induced by intraperitoneal injection of para-chlorophenylalanine. Model rats were randomly divided into model group（normal saline,2 mL/100 g）,positive control group（alprazolam,0.09 mg/kg）,water extract of Sugmel-3 decoction high-dose and low-dose groups（108.0,54.0 mg/kg）,with 10 rats in each group. Other 10 normal rats were included in blank group（normal saline,2 mL/100 g）. Other groups were given relevant medicine intragastrically once a day,and then sacrificed after consecutive administration of 7 d. ELISA assay was used to detect the contents of 5-HT,GABA,IL-1β,SOD and MDA in cerebral tissue of rats. RESULTS：In the experiment of sedation and hypnosis,compared with blank group,the activity time and the number of standings of mice in other groups were decreased significantly（P〈0.05 or P〈0.01）,sleep latency of mice was shortened significantly in water extract of Sugmel-3 decoction high-dosage group and positive control group（P〈0.05 or P〈0.01）. The sleep duration of mice was prolonged significantly in water extract high-dose group of Sugmel-3 decoction（P〈0.05）. In the experiment of hypnotic mechanism,compared with blank group,the contents of 5-HT,GABA and SOD in cerebral tissue of rats were decreased significantly in model group（P〈0.05）,the contents of IL-1 β and MDA were increased significantly（P〈0.05）. Compared with model group,the content of 5-HT of rats was increased significantly in positive control group,water extract of Sugmel-3 decoction high-dose and low-dose group（P〈0.05 or P〈0.01）. The contents of GABA and SOD in cerebral tissue of rats were increased significantly in water extract of Sugmel-3 decoction high-dose group and positive control group（P〈0.05 or P〈0.01）. The content of IL-1 β of rats in water extract of Sugmel-3 decoction high-dose and low-dose group were decreased significantly （P〈0.05）,the others indexes differences were not statistically significant （P〉0.05）. CONCLUSIONS：The water extract of Sugmel-3 decoction has good sedative and hypnotic effects,and its hypnotic mechanism may be related to the regulation of level of 5-HT and GABA in central neurotransmitters and the cytokine IL-1β.