人参皂苷Rg1的抗抑郁作用及其作用机制

摘要

Objective:To investigate the anti-depressive-like effects and mechanisms of Ginsenoside Rg1. Methods:Antidepressant-like effect of Ginsenoside Rg1 was assessed in mice tail suspension test and forced swim test,and trat chronic unpredictable mild stress (CUMS)(28 days)test. Rg1(5,10,20 mg·kg-1·d-1)and duloxetine(10 mg·kg-1·d-1)were studied. Results:Rg1(5,10,20 mg·kg-1)significantly reduced the immobility time in both forced swimming and tail suspension tests. In animals receiving CUMS,they showed an increased immobility in the forced swimming test and decreased sucrose preference test,and Rg1 produced a significant decrease of immobility time and an increase of sucrose intake percentage. The anti-depressive-like mechanisms of Rg1 involved the activation of cAMP signal transduction pathways induced by PDE4,and the increase of androgens level as well as the promotion of the synaptogenesis. Conclusion:Ginsenoside Rg1 has robust antidepressant-like effects in acute and chronic models of depression,and the underlying mechanisms could involve regulating neurotransmitter release,reducing glucocorticoid levels and increasing the expression of neurotrophic factors as well as enhancing synaptic plasticity.%目的：观察人参皂苷Rg1的抗抑郁作用，探讨其抗抑郁机制。方法：采用小鼠悬尾实验（tail suspension test，TST）和强迫游泳实验（forced swim test，FST）建立急性应激模型，选择大鼠慢性温和不可预见性应激（chronic unpredictable mild stress，CUMS）的方法建立长期抑郁模型。同时给予人参皂苷Rg1（5，10，20 mg·kg-1·d-1）和度洛西汀（10 mg·kg-1·d-1），观察Rg1的抗抑郁作用。结果：在急性应激实验中，Rg1三个剂量组（5，10，20 mg·kg-1）均能够显著减少动物的不动时间。慢性应激后，采用强迫游泳和糖水消耗实验进行行为学检测，与模型组相比，Rg1三个剂量均能够显著减少大鼠在强迫游泳实验中的不动时间，增加糖水偏好实验的糖水消耗百分比，延长动物的睡眠时间。机制研究证明，Rg1可抑制PDE4引起环腺苷酸（cyclic adenosine monophsphate，cAMP）的累积，进而激活cAMP介导的抗抑郁信号转导途径，还可增加雄激素水平，而雄激素又能拮抗糖皮质激素的释放和增加基础突触传递。此外，增加突触新生也是抗抑郁的重要机制。结论：人参皂苷Rg1对小鼠急性应激和CUMS诱导的大鼠抑郁行为有显著的改善作用，并可能通过调节神经递质和激素的释放、减少糖皮质激素含量、增加神经营养因子的表达以及增强突触可塑性来发挥抗抑郁作用。