枸杞籽油对CUS致小鼠应激行为的保护作用

Beneficial effects of Lycium barbarum seed oil on chronically stressed mice

目的探讨枸杞籽油(LBSO)对慢性应激所致小鼠抑郁样行为和认知功能障碍的保护作用及其机制。方法采用甲酯化反应联合GC-MS法测定LBSO的脂肪酸组成和比例。采用孤养结合建立小鼠慢性不可预见性应激模型,实验动物随机分为正常组、模型组、氟西汀组(20 mg·kg^(-1))、LBSO(2. 5、5. 0、10. 0 m L·kg-1)组。旷场、悬尾、强迫游泳和Morris水迷宫实验评价小鼠抑郁样行为和学习记忆能力;ELISA法检测血清皮质酮水平; Western blot法检测海马中BDNF、CREB和p-CREB的蛋白表达。结果本次实验从LBSO样品中分离得到(Z)-9-十八碳烯酸(66. 40%)、反式-9,12-十八碳二烯酸(21. 56%)和十七碳酸(5. 82%)等5个组分。LBSO干预能够提高CUS小鼠旷场实验运动得分,缩短悬尾实验及强迫游泳实验的不动时间,缩短水迷宫实验中的逃逸潜伏期、平均潜伏距离,增加其穿越平台有效次数;降低血清皮质酮水平;增加海马内BDNF蛋白表达及p-CREB/CREB的比值。结论 LBSO可改善慢性应激小鼠的抑郁样行为和认知功能障碍,其机制可能与降低血清皮质酮水平,上调海马内CREB-BDNF信号通路关键蛋白表达有关。

Aim To investigate the protective effect of Lycium barbarum seed oil(LBSO)on chronic unpredictable stress(CUS)induced depressant-like behavior and cognitive dysfunction in mice and its mechanism.Methods Constituent analysis of the fatty acids in LBSO was performed by methyl esterification plus GC-MS.Mice chronically stressed model was developed by CUS for28consecutive days in a solitary condition.Mice were randomly divided into normal control group,model group,fluoxetine plus CUS group(Flx,20mg·kg^-1),high-,middle-and low-doses of LBSO(10.0,5.0,2.5mL·kg^-1)plus CUS groups.The depressive symptoms were evaluated by open-field test(OFT),tail suspension test(TST)and forced-swimming test(FST);the learning and memory functions were tested by Morris water maze test(MWMT).Serum corticosterone level was assessed by ELISA.The protein expressions of BDNF,CREB and p-CREB in mouse hippocampus were determined by Western blot.Results Five components were isolated from LBSO samples,which were identified to be(Z)-9-octadecenoic acid(66.40%),9,12-octadecadienoic acid(21.56%),heptadecanoic acid(5.82%),octadecanoic acid(3.05%)and9-octadecenoic acid(1.92%).Compared with model group,LBSO could reduce the serum corticosterone level,improve OFT campaign scoring,reduce the immobility time in TST and FST,decrease the escape latency and the traveled distance in learning procedure in MWMT,and also increase the frequency to enter the target zone in Probe Trials in MWMT.In addition,LBSO significantly increased the expression of BDNF and p-CREB/CREB ratio in hippocampus in CUS mice.Conclusions LBSO could remarkably ameliorate the depressant-like behavior and cognitive dysfunction in chronically stressed mice,which may be due to its ability to reduce the serum corticosterone level and promote CREB-BDNF signaling pathway related protein expression in hippocampus.