Genovese Tiziana, Esposito Emanuela, Mazzon Emanuela, Di Paola Rosanna, Meli Rosaria, Bramanti Placido, Piomelli Daniele, Calignano Antonio, Cuzzocrea Salvatore
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
J Pharmacol Exp Ther. 2008 Jul;326(1):12-23. doi: 10.1124/jpet.108.136903. Epub 2008 Mar 26.
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-kappaB 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.
过氧化物酶体增殖物激活受体（PPAR）-α是核受体超家族的成员之一，其激活可调节与小鼠脊髓损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PPAR-α激活的机制减轻疼痛和炎症。本研究的目的是评估PEA对小鼠实验性脊髓损伤（SCI）诱导的继发性损伤的影响。通过四级T（5）-T（8）椎板切除术对硬脑膜应用血管夹诱导SCI。这导致了以水肿、中性粒细胞浸润、炎症介质产生、组织损伤和细胞凋亡为特征的严重创伤。重复给予PEA（10mg/kg腹腔注射；SCI前30分钟以及SCI后1小时和6小时）可显著降低：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-κB激活，6）诱导型一氧化氮合酶表达，以及6）细胞凋亡。此外，PEA治疗显著改善了运动肢体功能的恢复。总之，结果表明PEA减轻了与SCI相关的炎症和组织损伤，并提示内源性PPAR-α信号在与脊髓创伤相关的炎症反应中具有调节作用。
