Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury
Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury
复制标题
DOI：
10.1124/jpet.108.136903
复制
发表时间：
2008-07-01
影响因子：
3.5
通讯作者：
Cuzzocrea, Salvatore
中科院分区：
文献类型：
--
作者：
Genovese, Tiziana;Esposito, Emanuela;Cuzzocrea, Salvatore
核受体超家族成员过氧化物酶体增殖物激活受体（PPAR）-α的激活可调节小鼠脊髓创伤相关的炎症和组织损伤事件。棕榈酰乙醇胺（PEA）是棕榈酸和乙醇胺的天然酰胺，通过依赖于PPAR-alpha激活的机制减轻疼痛和炎症。本研究的目的是评价PEA对实验性脊髓损伤（SCI）所致继发性损伤的影响。通过四节段T-5-T-8椎板切除术将血管夹应用于硬脑膜诱导SCI。这导致以水肿、中性粒细胞浸润和炎症介质产生、组织损伤和细胞凋亡为特征的严重创伤。重复PEA给药（10 mg/kg i. p.;脊髓损伤前30 min和脊髓损伤后1 h和6 h）显著降低：1）脊髓炎症和组织损伤程度，2）中性粒细胞浸润，3）硝基酪氨酸形成，4）促炎细胞因子表达，5）核转录因子激活-κ B激活，6）诱导型一氧化氮合酶表达，6）细胞凋亡。此外，PEA治疗显著改善运动肢体功能的恢复。总之，结果表明PEA减少了与SCI相关的炎症和组织损伤，并表明内源性PPAR-alpha信号在与脊髓创伤相关的炎症反应中的调节作用。
Activation of peroxisome proliferator-activated receptor (PPAR)-alpha, a member of the nuclear receptor superfamily, modulates inflammation and tissue injury events associated with spinal cord trauma in mice. Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through a mechanism dependent on PPAR-alpha activation. The aim of the present study was to evaluate the effect of the PEA on secondary damage induced by experimental spinal cord injury (SCI) in mice. SCI was induced by application of vascular clips to the dura mater via a four-level T-5-T-8 laminectomy. This resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis. Repeated PEA administration (10 mg/kg i.p.; 30 min before and 1 and 6 h after SCI) significantly reduced: 1) the degree of spinal cord inflammation and tissue injury, 2) neutrophil infiltration, 3) nitrotyrosine formation, 4) proinflammatory cytokine expression, 5) nuclear transcription factor activation-kappa B activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis. Moreover, PEA treatment significantly ameliorated the recovery of motor limb function. Together, the results indicate that PEA reduces inflammation and tissue injury associated with SCI and suggest a regulatory role for endogenous PPAR-alpha signaling in the inflammatory response associated with spinal cord trauma.