N-棕榈酰乙醇胺通过调控前额叶皮质PPARα通路抗大鼠抑郁样行为  

Antidepressant-like effect of N-palmitoylethanolamide by prefrontal cortex PPARα pathway in a rat model

作　　者：唐文娟 范红艳 张露文 姜正二[1] 于海玲[1] TANG Wen-juan;FAN Hong-yan;ZHANG Lu-wen;JIANG Zheng-er;YU Hai-ling(College of Medicine,Yanbian University,Yanji 133002,China;Department of Pharmacology,College of Basic Medicine,Jilin Medical University,Jilin 132013,China)

机构地区：[1]延边大学医学院,吉林延吉133000 [2]吉林医药学院基础医学院药理学教研室,吉林吉林132013

出　　处：《中国病理生理杂志》2020年第3期451-460,共10页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81760650,No.81460217)。

摘　　要：目的:探讨皮质过氧化物酶体增殖物激活受体α(PPARα)在N-棕榈酰乙醇胺(PEA)调控大鼠抑郁样行为中的作用。方法:构建大鼠慢性不可预见性温和应激(CUMS)抑郁模型。将70只大鼠随机分为正常对照组、CUMS模型组、CUMS+氟西汀(10 mg/kg)组、CUMS+PEA (2.5、5和10 mg/kg)组及CUMS+PEA (10 mg/kg)+MK886 (3 mg/kg)组。CUMS第8天开始药物处理,监测大鼠体重并测试其相关行为学变化。第36天大鼠麻醉后取脑组织标本,用免疫组化和组织形态学方法观察前额叶皮质(PFC)的突触小泡蛋白(SYP)表达及神经元形态改变;Western blot和RT-PCR法检测大鼠PFC中PPARα蛋白和mRNA的表达。结果:PEA增加CUMS抑郁模型大鼠的体重获得、蔗糖偏好率和旷场实验中的运动时间,缩短旷场实验的不动时间(P<0.01),上调PFC中SYP的蛋白表达,改善神经元的形态,增加PFC质量及PFC/全脑百分比,下调PFC中PPARα的蛋白和mRNA表达。与PEA(10 mg/kg)的组相比,MK886组大鼠在CUMS第35天体重获得和蔗糖偏好率明显降低,旷场实验中不动时间增加及运动距离减少,PFC中的SYP表达降低,PPARα的蛋白和mRNA表达上调(P<0.05)。结论:PEA拮抗CUMS大鼠的抑郁样行为,其机制可能与PEA调控PFC的PPARα通路、改善其突触可塑性有关。AIM: To investigate the role of cortical peroxisome proliferator-activated receptor α(PPARα) in the regulation of depression-like behavior in the rats by N-palmitoylethanolamide(PEA). METHODS: A rat model of chronic unpredictable mild stress(CUMS) was established. The rats(n=70) were randomly divided into normal control group, CUMS model group, CUMS+fluoxetine(10 mg/kg) group, CUMS+PEA(2.5, 5 and 10 mg/kg) groups and CUMS+PEA(10 mg/kg)+MK886(3 mg/kg) group. On the 8 th day during CUMS, the drugs were continuously admi-nistered for 28 d. The body weight and the related behavioral changes in the open-field test and sucrose consumption test were monitored every week. On the 36 th day, some of the brain tissues from the rats were fixed in 4% formalin solution for histomorphological and immunohistochemical observations to determine the number and morphological changes of prefrontal cortex(PFC) neurons and the protein expression of synaptophysin(SYP).Other brain tissues were quickly removed, PFC was separated and weighed, and Western blot and RT-PCR were used to detect the expression of PPARα at protein and mRNA levels in the PFC of rats. RESULTS: Compared with CUMS model group, PEA increased the body weight gain, the sucrose preference rate, and the locomotion time and distance in the open-field test, and shortened the immobility time in the open-field test. PEA increased the weight of PFC, the percentage of PFC/brain weight and the number of neurons in PFC, and improved the morphological changs of the neurons. PEA also up-regulated the protein expression of SYP in PFC, and down-regulated the expression of PPARα at mRNA and protein levels in the PFC of CUMS model rats(P<0.05). In addition, compared with PEA(10 mg/kg) group, MK886 significantly reduced the body weight gain of the rats, the percentage of sucrose preference and the locomotion distance in the open-field test, and increased the immobility time in the open-field test on the 35 th day during CUMS. The number of neurons SYP expression in PFC tissues were

关 键 词：N-棕榈酰乙醇胺 抑郁症 慢性不可预见性温和应激 过氧化物酶体增殖物激活受体Α 前额叶皮质 

分 类 号：R964[医药卫生—药理学] R363[医药卫生—药学]