天津医药

天津医药 ›› 2022, Vol. 50 ›› Issue (3): 248-253.doi: 10.11958/20211792

• 实验研究 • 上一篇    下一篇

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

李瑞瑞，张露文，张渺，于海玲   

  1. 延边大学医学院（邮编133000）
  • 收稿日期:2021-08-09 修回日期:2021-12-19 出版日期:2022-03-15 发布日期:2022-03-15
  • 基金资助:
    国家自然科学基金地区基金项目（81760650，81960656）

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

LI Ruirui, ZHANG Luwen, ZHANG Miao, YU Hailing   

  1. College of Medicine, Yanbian University, Yanji 133000, China
  • Received:2021-08-09 Revised:2021-12-19 Published:2022-03-15 Online:2022-03-15

PDF (PC)

2625

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+MK886 3 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（TNF-α）、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。

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

Abstract: 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+MK886 3 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 brain-derived 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-1β and 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-1β and NF-κB of prefrontal cortex or hippocampus. Conclusion　PEA plays a neuroprotective role by regulating PPARα pathway in prefrontal cortex and hippocampus to promote neural plasticity, relieve neuroinflammation, thus improving depression like behavior in CUMS rats.

Key words: depressive disorder, hippocampus, N-palmitoylethanolamine, prefrontal cortex, peroxisome proliferator-activated receptor alpha