酸枣仁合欢方皂苷部位及其主要成分对CUMS抑郁失眠小鼠的影响

The Effect of Suanzaoren Hehuan Formula Effective Fraction and Its Main Components on Depression and Insomnia Relieving in CUMS Model Mice

目的探讨酸枣仁合欢方(SHF)皂苷部位及其主要成分白桦脂酸、白桦脂醇对慢性不可预期温和应激(CUMS)抑郁失眠模型小鼠的影响。方法采用21 d不可预期温和刺激复制CUMS抑郁失眠小鼠模型。小鼠随机分为空白组、模型对照组、文拉法辛组(9.38 mg·kg^-1)、解郁安神组(650 mg·kg^-1)、SHF皂苷组(30 mg·kg^-1)、白桦脂醇组(4 mg·kg^-1)和白桦脂酸组(12 mg·kg^-1),每组10只。灌胃给药,每日1次,持续21 d。进行行为学观测实验:悬尾试验、强迫游泳试验、阈上剂量戊巴比妥钠睡眠试验;采用荧光分光光度法测定小鼠脑组织中海马及皮层区域的多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)等脑内单胺神经递质的含量。结果与模型对照组比较,SHF皂苷组小鼠的TST不动时间、FST不动时间显著减少(P<0.01),睡眠潜伏期时间显著缩短(P<0.01),阈上剂量戊巴比妥钠所致睡眠时间明显延长(P<0.05),小鼠海马、大脑皮层组织的5-HT含量显著升高(P<0.05,P<0.01);白桦脂酸组小鼠的FST不动时间显著减少(P<0.05),睡眠潜伏期时间显著缩短(P<0.01),阈上剂量戊巴比妥钠所致睡眠时间明显延长(P<0.01),大脑皮层组织的5-HT含量显著升高(P<0.05);白桦脂醇组小鼠的睡眠潜伏期时间显著缩短(P<0.01),大脑皮层组织的5-HT含量显著升高(P<0.05)。结论SHF皂苷部位及其主要成分白桦脂醇、白桦脂酸具有抗抑郁、镇静催眠的作用,白桦脂醇、白桦脂酸可作为SHF解郁安神的有效成分作进一步研究。

Objective To investigate the antidepressant and tranquilizing effect of Suanzaoren Hehuan Formula(SHF)saponins and the main components(betulinic acid and betulin)on CUMS model mice with depression and insomnia.Methods CUMS depression and insomnia mouse models were established by 21 days of unexpected mild stimulation.The mice were randomly divided into Blank group,Model group,Venlafaxine group(9.38 mg·kg^-1),Jieyu Anshen group(650 mg·kg^-1),SHF saponin group(30 mg·kg^-1),Betulin group(4 mg·kg^-1)and Betulinic acid group(12 mg·kg^-1),10 rats in each group.The drugs were given intragastrically once a day for 21 days.The differences of mice in each group were observed by tail suspension test,forced swimming test,and supraliminal dose pentobarbital sodium sleep test.The contents of monoamine neurotransmitters such as dopamine(DA),norepinephrine(NE)and 5-hydroxytryptamine(5-HT)in hippocampus and cortex of mice were determined by fluorescence spectrophotometry.Results Compared with the Model group,the TST immobile time,FST immobile time and the sleep latency time of SHF saponin group were significantly decreased,and the differences were statistically significant(P<0.01).The sleep time induced by pentobarbital sodium at the supraliminal dose(40 mg·kg^-1)in SHF saponin group was prolonged compared with the Model group(P<0.05).The levels of 5-HT were sharply risen in hippocampus(P<0.05)and cortex(P<0.01).In betulinic acid group,FST immobility time and sleep latency time induced by supraliminal dose of pentobarbital sodium were significantly decreased(P<0.05,P<0.01),and sleep time was significantly prolonged(P<0.01).The content of 5-HT in cerebral cortex was significantly increased(P<0.05).In betulin group,the sleep latency time was significantly shortened(P<0.01)and the content of 5-HT in cortex was significantly increased(P<0.05).Conclusion SHF saponins have antidepressant,sedative and hypnotic effects.Betulin and betulinic acid,the main components of SHF saponins,also have the effect of relieving depression and tranquilizing nerves,which can be used as the effective components of SHF for further research.