N-棕榈酰乙醇胺通过PPARα途径阻断慢性应激诱导的大鼠抑郁样作用研究

α型过氧化物酶体增殖物激活受体 (Peroxisome proliferator-activated receptor-alpha, PPARα)是配体活化的转录因子。N-棕榈酰乙醇胺（N-palmitoylethanolamide, PEA）是PPARα的内源性配体，为内源性大麻素样物质。申请人前期研究发现PEA可明显拮抗由强迫游泳导致的动物不动时间延长，提示PEA具有抗抑郁样作用，但其作用机制和靶点尚不清楚。因此，本课题拟应用高效液相分析、分子生物学、组织病理学和行为学等技术手段研究PEA对抑郁模型大鼠海马、前额叶皮质PPARα、PPARα mRNA、脑源性神经营养因子（BDNF）表达，神经元细胞凋亡率、形态、超微结构，及大鼠相关行为学改变等的影响，阐明内源性大麻素样物质PEA活化PPARα途径是否是其阻断慢性应激诱导的大鼠抑郁样行为的作用靶点，为抑郁症的临床药物治疗提供新思路。

Peroxisome proliferator-activated receptor-alpha (PPARα), is a ligand-activated transcription factor. N-palmitoylethanolamide (PEA) is the endogenous ligand of PPARα, is also an endocannabinoid analogue and endogenous lipid compound secreted by human fat-storing cells. The applicant's preliminary study found that PEA can significantly antagonized the the forced swimming-induced increase in immobility in mice, suggesting that the PEA have an antidepressant-like effect. However, the mechanisms and targets of the PEA-induced antidepression are unclear. In the present study, we will use HPLC analysis, immunohistochemistry, flow cytometry technique, molecular biology, histopathology and behavior methods, to study the effects of PEA of PPARα, brain original nerve growth factor (BDNF), nerve growth factor (NGF), poly-sialic acid neural cell adhesion molecule (PSA-NCAM) and other content or activity. We aim to clarify the possible targets mediated by PPARα pathway of PEA on the antidepressant-like effect, and provide a new way of medication for clinical depression.