神经药理学报
神經藥理學報
신경약이학보
Journal of Hebei North University(Medical Edition)
2013年
1期
1-11
,共11页
黄倩%楚世峰%连晓媛%张均田
黃倩%楚世峰%連曉媛%張均田
황천%초세봉%련효원%장균전
抑郁%人参皂苷Rg1%急性应激%慢性温和不可预知性应激%糖皮质激素%突触可塑性
抑鬱%人參皂苷Rg1%急性應激%慢性溫和不可預知性應激%糖皮質激素%突觸可塑性
억욱%인삼조감Rg1%급성응격%만성온화불가예지성응격%당피질격소%돌촉가소성
depression%ginsenoside Rg1%acute stress%chronic unpredictable mild stress%glucocorticoid%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。
目的:觀察人參皂苷Rg1的抗抑鬱作用,探討其抗抑鬱機製。方法:採用小鼠懸尾實驗(tail suspension test,TST)和彊迫遊泳實驗(forced swim test,FST)建立急性應激模型,選擇大鼠慢性溫和不可預見性應激(chronic unpredictable mild stress,CUMS)的方法建立長期抑鬱模型。同時給予人參皂苷Rg1(5,10,20 mg·kg-1·d-1)和度洛西汀(10 mg·kg-1·d-1),觀察Rg1的抗抑鬱作用。結果:在急性應激實驗中,Rg1三箇劑量組(5,10,20 mg·kg-1)均能夠顯著減少動物的不動時間。慢性應激後,採用彊迫遊泳和糖水消耗實驗進行行為學檢測,與模型組相比,Rg1三箇劑量均能夠顯著減少大鼠在彊迫遊泳實驗中的不動時間,增加糖水偏好實驗的糖水消耗百分比,延長動物的睡眠時間。機製研究證明,Rg1可抑製PDE4引起環腺苷痠(cyclic adenosine monophsphate,cAMP)的纍積,進而激活cAMP介導的抗抑鬱信號轉導途徑,還可增加雄激素水平,而雄激素又能拮抗糖皮質激素的釋放和增加基礎突觸傳遞。此外,增加突觸新生也是抗抑鬱的重要機製。結論:人參皂苷Rg1對小鼠急性應激和CUMS誘導的大鼠抑鬱行為有顯著的改善作用,併可能通過調節神經遞質和激素的釋放、減少糖皮質激素含量、增加神經營養因子的錶達以及增彊突觸可塑性來髮揮抗抑鬱作用。
목적:관찰인삼조감Rg1적항억욱작용,탐토기항억욱궤제。방법:채용소서현미실험(tail suspension test,TST)화강박유영실험(forced swim test,FST)건립급성응격모형,선택대서만성온화불가예견성응격(chronic unpredictable mild stress,CUMS)적방법건립장기억욱모형。동시급여인삼조감Rg1(5,10,20 mg·kg-1·d-1)화도락서정(10 mg·kg-1·d-1),관찰Rg1적항억욱작용。결과:재급성응격실험중,Rg1삼개제량조(5,10,20 mg·kg-1)균능구현저감소동물적불동시간。만성응격후,채용강박유영화당수소모실험진행행위학검측,여모형조상비,Rg1삼개제량균능구현저감소대서재강박유영실험중적불동시간,증가당수편호실험적당수소모백분비,연장동물적수면시간。궤제연구증명,Rg1가억제PDE4인기배선감산(cyclic adenosine monophsphate,cAMP)적루적,진이격활cAMP개도적항억욱신호전도도경,환가증가웅격소수평,이웅격소우능길항당피질격소적석방화증가기출돌촉전체。차외,증가돌촉신생야시항억욱적중요궤제。결론:인삼조감Rg1대소서급성응격화CUMS유도적대서억욱행위유현저적개선작용,병가능통과조절신경체질화격소적석방、감소당피질격소함량、증가신경영양인자적표체이급증강돌촉가소성래발휘항억욱작용。
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.