皮质前额叶和海马PPAR-α通路参与N-棕榈酰乙醇胺抗大鼠抑郁样行为  

Prefrontal cortex and hippocampal PPAR-αpathway participate in N-palmitoylethanolamine anti-depression-like behaviors in rats

作　　者：李瑞瑞 张露文 张渺 于海玲[1] LI Ruirui;ZHANG Luwen;ZHANG Miao;YU Hailing(College of Medicine,Yanbian University,Yanji 133000,China)

机构地区：[1]延边大学医学院,133000

出　　处：《天津医药》2022年第3期248-253,共6页Tianjin Medical Journal

基　　金：国家自然科学基金地区基金项目(81760650,81960656)。

摘　　要：目的探讨皮质前额叶(PFC)和海马中α型过氧化物酶体增殖物激活受体(PPARα)参与N-棕榈酰乙醇胺(PEA)调控慢性应激诱导大鼠抑郁样行为的机制。方法将50只SD大鼠按照随机数字表法分为正常对照组、模型组、氟西汀组(阳性药物对照,10 mg/kg)、PEA组(10 mg/kg)和PEA+MK886组(PEA 10 mg/kg+MK8863 mg/kg),每组10只。除正常对照组外,其余各组大鼠给予慢性不可预见性温和应激(CUMS)和孤养应激干预4周建立抑郁模型,建模1周时分组给予相应药物干预4周。第36天麻醉大鼠后取脑组织标本,通过免疫组化染色观察皮质前额叶(PFC)和海马中多唾液酸-神经细胞黏附分子(PSA-NCAM)蛋白表达情况;酶联免疫吸附试验(ELISA)检测大鼠PFC中脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)的表达,及PFC和海马中肿瘤坏死因子-α(TNFα)、白细胞介素1β(IL-1β)和核转录因子-κB(NF-κB)的水平。结果PEA上调了CUMS抑郁模型大鼠PFC和海马中PSA-NCAM及PFC中BDNF和GDNF蛋白表达,下调了PFC和海马中TNF-α、IL-1β和NF-κB水平。与PEA组相比,PEA+MK886组大鼠PFC和海马中PSA-NCAM、PFC中BDNF和GDNF的表达下调,PFC和海马中TNF-α、IL-1β、NF-κB的水平增加。结论PEA可通过调控PFC和海马的PPARα通路促进神经可塑性、缓解神经炎症,发挥神经保护作用,从而改善CUMS大鼠的抑郁样行为。Objective To investigate the role of N-palmitoylethanolamide(PEA)in regulating the depression-like behavior induced by chronic stress in rats,which is mediated by a potential target peroxisome proliferator-activated receptor alpha(PPARα)of prefrontal cortex(PFC)and hippocampus.Methods Fifty SD rats are randomly divided into the normal control group,the chronic unpredictable mild stress(CUMS)model group,the fluoxetine group(positive drug control,10 mg/kg),the PEA group(10 mg/kg),and the PEA+MK886 group(PEA 10 mg/kg+MK8863 mg/kg).In addition to the normal control group,other groups were given CUMS intervention for 4 weeks to establish depression model.After 1 week of modeling,groups were given corresponding drug intervention for 4 weeks.On the thirty-sixth day,after rats were anesthetized and sacrificed,the prefrontal cortex and hippocampus were quickly separated and preserved.The expression of polysialic acid-nerve cell adhesion molecule(PSA-NCAM)protein in cortex prefrontal lobe(PFC)and hippocampus was observed by immunohistochemical method.The enzyme-linked immunosorbent assay(ELISA)was used to detect brainderived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and nuclear transcription factor(NF-κB)levels in rat PFC or hippocampus.Results Compared with the CUMS model group,PEA up-regulated the protein expression of PSA-NCAM in prefrontal cortex and hippocampus,and BDNF and GDNF in prefrontal cortex,and down-regulated the levels of TNF-α,IL-1βand NF-κB in prefrontal cortex and hippocampus in the PEA group.Compared with the PEA group,the rats in the MK886 group down-regulated protein expression levels of PSA-NCAM,BDNF and GDNF,and up-regulated the levels of TNF-α,IL-1βand NF-κB of prefrontal cortex or hippocampus.Conclusion PEA plays a neuroprotective role by regulating PPARαpathway in prefrontal cortex and hippocampus to promote neural plasticity,relieve neuroinflammation,thus improving depression like behavior in CUMS rats.

关 键 词：抑郁症 海马 N-棕榈酰乙醇胺 皮质前额叶 过氧化物酶体增殖物激活α受体 

分 类 号：R964[医药卫生—药理学]