佛手挥发油的抗抑郁作用机制探讨

Antidepressant Effect of Fingered Citron Volatile in Rats

目的:在探讨佛手挥发油对慢性应激所致大鼠抑郁模型(CUMS)的干预作用。方法:90只Wistar大鼠随机分为6组,每组15只,分别为空白对照组、模型组、阳性药组(10 mg.kg-1氟西汀ig 21 d)、佛手挥发油低、中、高剂量(150,300,600mg.kg-1佛手挥发油ig 21 d)。除空白对照组外,其余5组大鼠经历21 d慢性应激造成抑郁模型,各组大鼠造模同时给予相应药物。21 d慢性应激后以糖水偏爱和旷场测试测定动物的行为变化,放免法测定大鼠血清中皮质酮(CORT)水平,蛋白免疫印迹法测定脑组织神经营养因子(BDNF)的蛋白表达水平。结果:与正常组大鼠比较,模型组经过慢性应激3周后大鼠糖水偏好由(88.1±13.3)%降至(60.5±9.8)%,旷场水平评分及垂直评分分别由(123.5±21.3)和(38.2±5.9)降为(72.5±12.7)和(17.1±5.1),表明慢性应激导致大鼠产生抑郁样行为;同时,抑郁大鼠的血清CORT水平由(42.1±7.7)μg.L-1增加为(117.6±19.3)μg.L-1,海马BDNF表达水平由(0.22±0.04)降为(0.07±0.02)。佛手挥发油干预治疗后能呈剂量依赖地改善由慢性应激所致的大鼠抑郁行为及生化指标改变。其中300,600 mg.kg-1佛手挥发油组糖水偏好分别为(70.7±10.2)%和(77.1±11.9)%,与抑郁组比较有显著的统计学差异(分别为P<0.05和P<0.01);150,300,600 mg.kg-1佛手挥发油组旷场水平评分分别为(87.7±15.4),(98.3±19.7),(110.3±28.9),与抑郁组比较有显著差异(P<0.05,P<0.01);300,600 mg.kg-1佛手挥发油组旷场垂直评分分别为(24.5±6.3),(29.2±7.2),与抑郁组比较有显著差异(P<0.05,P<0.01);皮质酮浓度分别为(90.1±13.5),(77.5±10.7)μg.L-1,与抑郁组比较有显著差异(P<0.05,P<0.01);300,600 mg.kg-1佛手挥发油组海马BDNF相对含量为(0.15±0.03)和(0.18±0.03),与抑郁组比较有显著的统计学差异(分别为P<0.05和P<0.01)。结论:佛手挥发油的抗抑郁作用机制可能与调节血清CORT水平和海马组织BDNF表达水平有关。

Objective：Previous studies have demonstrated that fingered citron volatile produced antidepressant-like action in various mouse models with behavioral despair.The present study aimed to examine whether fingered citron volatile could affect the chronic unpredictable mild stress（CUMS）-induced depression in rats.Method： Ninety male Wistar rats were randomly divided into six groups as follows： control,model,positive control（orally given fluoxetine 10 mg·kg-1 for 21 days）,low,middle and high dosages of fingered citron volatile（orally given 150,300,600 mg·kg-1 of fingered citron volatile for 21 days）.All groups except control were exposed to chronic stress for 21 days to establish depression model and every rat was given corresponding drugs simultaneously.After 21 days,the behavior changes were measured by sucrose preference and open-field,serum corticosterone level was measured by radio-immunity and brain-derived neurotrophic factor（BDNF） protein levels was measured by Western-blot.Result： CUMS being lasted for 3 weeks,caused depression-like behavior in rats,as indicated by the significant decrease in sucrose preference（from 88.1%±13.3% to 60.5%±9.8 %） and in open-field scores（from 123.5±21.3 to 38.2±5.9 and from 72.5±12.7 to 17.1±5.1,respectively）.Whereas serum corticosterone level was significantly increased in rats exposed to CUMS [from（42.1±7.7） μg·L-1 to（117.6±19.3） μg·L-1],and BDNF protein expression were decreased（from 0.22±0.04 to 0.07±0.02） in CUMS-treated rats.Daily intragastric administration of fingered citron volatile（150,300,600 mg·kg-1） during the three weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS.As the sucrose preferences in 300,600 mg·kg-1 fingered citron volatile were 70.7%±10.2 % and 77.1%±11.9 %（P0.05 and P0.01）;the horizontal scores in 150,300,600 mg·kg-1 fingered citron volatile were 87.7±15.4,98.3±19.7 and 110.3±28.9（P0.05,P0.05 and P0.01）;the vertical scores in 300,600 mg·kg-1 fingered citron volatile were 24.5±6.3 and 29.2±7.2（P0.05 and P0.01）;the serum corticosterone levels in 300,600 mg·kg-1 fingered citron volatile were（90.1±13.5） μg·L-1 and（77.5±10.7） μg·L-1（P0.05 and P0.01）;the BDNF levels in 300,600 mg·kg-1 fingered citron volatile were 0.15±0.03 and 0.18±0.03（P0.05 and P0.01）.Conclusion： The results suggest that the antidepressant-like actions of fingered citron volatile may be mediated by modulating the CORT concentration and increasing the expression of BDNF in hippocampus tissues.