N-棕榈酰乙醇胺对慢性束缚应激小鼠焦虑抑郁样行为的影响

发布时间：2018-02-22 09:00

本文关键词： N-棕榈酰乙醇胺束缚应激焦虑抑郁　出处：《中国病理生理杂志》2017年03期 　论文类型：期刊论文

【摘要】：目的:采用慢性束缚应激小鼠模型,研究N-棕榈酰乙醇胺(N-palmitoylethanolamide,PEA)对小鼠焦虑抑郁样行为的影响,进一步探讨PEA抗小鼠焦虑抑郁作用的可能机制。方法:小鼠分为正常对照组、模型组、氟西汀(10 mg/kg)组和PEA 2.5、5、10 mg/kg组,每天灌胃给药后30 min,将小鼠(除了正常对照组)放置于有机玻璃管内接受4 h的慢性束缚应激,持续21 d。第22天采用旷场实验和强迫应激实验观察PEA对慢性束缚应激小鼠抑郁样行为的影响;高架十字迷宫实验探讨PEA对慢性束缚应激小鼠焦虑样行为的影响;水迷宫方法分析PEA对慢性束缚应激小鼠学习、记忆、空间定向和认知功能等方面的作用;ELISA方法检测慢性束缚应激小鼠血清促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质醇(cortisol,CORT)及海马5-羟色胺(5-hydroxytryptamine,5-HT)含量的变化;可见分光光度法检测海马乙酰胆碱酯酶(acetylcholinesterase,ACh E)活性的改变。结果:与模型组相比,在小鼠强迫应激实验中,PEA及氟西汀组小鼠不动时间明显减少;旷场试验中,PEA及氟西汀明显增加小鼠水平移动距离及运动总时间,但只有PEA 10 mg/kg及氟西汀组增加了小鼠直立次数;在高架十字迷宫实验中,PEA及氟西汀明显增加小鼠开臂进入次数、开臂停留时间百分比及在臂总移动距离;在水迷宫实验中,PEA 5、10mg/kg及氟西汀组明显缩短小鼠寻台潜伏期,PEA 10 mg/kg及氟西汀组明显缩短小鼠搜寻距离。与应激模型组比较,PEA 2.5~10 mg/kg及氟西汀显著降低小鼠血清中ACTH水平,PEA 5、10 mg/kg及氟西汀显著降低小鼠血清CORT水平及小鼠肾上腺指数,PEA 10 mg/kg及氟西汀显著增高海马5-HT含量,降低海马ACh E活性,但PEA 2.5和5 mg/kg组海马组织中5-HT含量及ACh E活性则无明显改变。结论:PEA对束缚应激模型小鼠的焦虑及抑郁样行为具有一定的拮抗作用,其具体作用机制可能与调节下丘脑-垂体-肾上腺轴功能、增加海马单胺类递质5-HT水平及参与中枢胆碱系统的调节有关。
[Abstract]:Objective: to study the effect of N-palmitosanolide PEAA on anxiety and depression-like behavior in mice under chronic restraint stress, and to explore the possible mechanism of anti-anxiety and depression in PEA mice. Methods: the mice were divided into normal control group. The model group, 10 mg / kg fluoxetine group and PEA 2.5 mg / kg 10 mg/kg group were given intragastric administration for 30 minutes daily. Mice (except the normal control group) were placed in the plexiglass tube for 4 hours under chronic restraint stress. On the 22nd day, the effects of PEA on depressive behavior of chronic restraint stress mice were observed by open field test and forced stress test, and the effects of PEA on anxiety like behavior of chronic restraint stress mice were investigated by elevated cross maze test. Water maze method was used to analyze the effects of PEA on learning and memory in mice with chronic restraint stress. The effects of spatial orientation and cognitive function were evaluated by Elisa. The changes of serum adrenocorticotropic hormone (ACTH), cortisol cortisol (Cort) and hippocampal 5-hydroxytryptamine 5-HT (5-HT) in chronic restraint stress mice were detected by enzyme-linked immunosorbent assay (Elisa). The activity of acetylcholinesterase acetylcholinesterase (acetylcholinesterase ACHE) in hippocampus was detected by spectrophotometry. Results: compared with the model group, the immobility time of PEA and fluoxetine groups was significantly decreased compared with the model group. In open field test, PEA and fluoxetine significantly increased the horizontal movement distance and total exercise time of mice, but only PEA 10 mg/kg and fluoxetine groups increased the number of mice standing upright. In the elevated cross maze test, PEA and fluoxetine significantly increased the number of open arm entry, the percentage of open arm retention time and the total distance of movement in the arm. In the water maze test, the PEA 5mg / kg and fluoxetine group significantly shortened the latency of searching for the platform and the search distance of the mice in the fluoxetine group and the PEA 10 mg / kg group. Compared with the stress model group, PEA 2.5 + 10 mg/kg and fluoxetine significantly decreased the ACTH water in the serum of the mice. PEA 5 + 10 mg/kg and fluoxetine significantly decreased the level of serum CORT and the adrenal index of mice, PEA 10 mg/kg and fluoxetine significantly increased the content of 5-HT in hippocampus. The activity of ACh E in hippocampus was decreased, but the content of 5-HT and the activity of ACh E in hippocampal tissue of PEA 2.5 and 5 mg/kg groups were not significantly changed. Conclusion: ACh has a certain antagonistic effect on anxiety and depressive behavior of restraint stress model mice. The mechanism may be related to regulating the hypothalamus-pituitary-adrenal axis function, increasing the level of monoamine neurotransmitter 5-HT in the hippocampus and participating in the regulation of the central choline system.
【作者单位】：延边大学医学院;延边大学药学院;
【基金】：国家自然科学基金资助项目(No.81460217)
【分类号】：R749

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