逍遥舒心胶囊对慢性应激抑郁模型小鼠的抗抑郁作用及其机制

Antidepressant Effect and Mechanism of Xiaoyao Shuxin Capsule on Mice Model of Chronic Stress-induced Depression

目的:探讨逍遥舒心胶囊对慢性应激抑郁模型小鼠的抗抑郁作用及可能机制。方法:60只ICR小鼠随机分为6组:正常对照组、模型组、逍遥丸(1.5 g·kg-1)组、逍遥舒心胶囊低、中、高剂量(0.5,1.5,4.5 g·kg-1)组。于造模第1天灌胃给药,每日1次,连续5周,空白对照组和模型组给予等容积的生理盐水。除空白对照组外,其余组均采用慢性不可预见性应激加孤养法建立慢性应激抑郁症小鼠模型,并观察逍遥舒心胶囊对小鼠强迫游泳和自主活动等指标的影响。采用分光光度法测定血清中超氧化物歧化酶(SOD)活力以及丙二醛(MDA)含量,采用酶联免疫吸附法测定脑组织中5-羟色胺(5-HT)、促肾上腺皮质激素(ACTH)、脑源性神经营养因子(BDNF)含量。结果:逍遥丸1.5 g·kg-1剂量及逍遥舒心胶囊1.5,4.5 g·kg-1剂量可缩短抑郁症小鼠游泳不动时间,使血清中SOD活力升高,MDA含量降低,并可升高脑组织中5-HT,BDNF含量,降低ACTH含量。逍遥丸1.5 g·kg-1剂量及逍遥舒心胶囊0.5,1.5,4.5 g·kg-1剂量组均可不同程度地提高抑郁症小鼠的自主活动次数,改善抑郁症症状。结论:逍遥舒心胶囊可拮抗慢性应激所引起的抑郁样行为,其作用机制可能与提高脑组织中单胺类神经递质功能,改善下丘脑-垂体-肾上腺(HPA)轴功能紊乱,提高神经可塑性和促进神经发生,改善机体自由基损伤等多种途径有关。

Objective： To investigate the antidepressant effect of Xiaoyao Shuxin capsule （XYSX） and its possible mechanism. Method： Sixty ICR mice were randomly divided into six groups：normal control group,model group,Xiaoyao Wan （1.5 g kg-1） group and XYSX（0.5,1.5,4.5 g kg-1） group. Except the normal control group,the other groups were treated with the chronic unpredictable mild stress stimulation （CUMS） combined with lonely raising for 35 d. Then the forced swimming test and free-activity test were carried out. The activity of superoxide dismutase（SOD） and the content of malondialdehyde（MDA） in blood serum were measured by the UV-spectrophotometric determination method and the content of serotonin（5-HT）,adrenocorticotropic hormone（ACTH） and brain-derived neurotrophic factor（BDNF） in brain were determined by ELISA. Result： XYSX （1.5,4.5 g kg-1） could reduce the time of immovability of the depressed mice,increase the activity of SOD,reduce the content of MDA in depressed mice,increase the content of 5-HT and BDNF and decrease the content of ACTH in the brain of the depressed mice. XYSX （0.5,1.5,4.5 g kg-1） could increase the time of free-activity. Conclusion： XYSX has a prominent therapeutic effect on mice model of chronic stress-induced depression and the mechanism might be related with the reduction of the content of monoamine neurotransmitters,the hyperfunction of hypothalamus-pituitary-adrenal（HPA）,the improvement of the neural plasticity and free radical damage.