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首页> 外文期刊>Journal of neuroinflammation >Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
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Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma

机译：PPAR-δ和PPAR-γ参与脊髓损伤后棕榈酰乙醇酰胺的抗炎和神经保护活性的分子证据

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Background Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. Moreover, several data have suggested that PEA reduced inflammation and tissue injury associated with spinal cord trauma and showed a regulatory role for peroxisome proliferator-activated receptor (PPAR)-α signaling in the neuroprotective effect of PEA. However, several other mechanisms could explain the anti-inflammatory and anti-hyperalgesic effects of PEA, including the activation of PPAR-δ and PPAR-γ. The aim of the present study was to carefully investigate the exact contribution of PPAR-δ and PPAR-γ in addition to PPAR-α, in the protective effect of PEA on secondary inflammatory damage associated with an experimental model of spinal cord injury (SCI). Methods SCI was induced in mice through a spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy, and PEA (10 mg/kg, intraperitoneally, 1 and 6 hours after SCI) was injected into wildtype mice and into mice lacking PPAR-α (PPAR-αKO). To deepen the ability of specific PPAR-δ and PPAR-γ antagonists to reverse the effect of PEA, mice were administered GSK0660 or GW9662, 30 minutes before PEA injection. Results Genetic ablation of PPAR-α in mice exacerbated spinal cord damage, while PEA-induced neuroprotection seemed be abolished in PPARαKO mice. Twenty-four hours after spinal cord damage, immunohistological and biochemical studies were performed on spinal cord tissue. Our results indicate that PPAR-δ and PPAR-γ also mediated the protection induced by PEA. In particular, PEA was less effective in PPAR-αKO, GSK0660-treated or GW9662-pretreated mice, as evaluated by the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, proinflammmatory cytokine, inducible nitric oxide synthase expression and motor function. PEA is also able to restore PPAR-δ and PPAR-γ expression in spinal cord tissue. Conclusion This study indicates that PPAR-δ and PPAR-γ can also contribute to the anti-inflammatory activity of PEA in SCI.
机译：背景技术棕榈酰乙醇酰胺（PEA）是一种内源性脂肪酸酰胺，具有抗炎和止痛作用。此外，一些数据表明，PEA减少了与脊髓损伤相关的炎症和组织损伤，并在PEA的神经保护作用中显示了过氧化物酶体增殖物激活受体（PPAR）-α信号的调节作用。但是，其他几种机制也可以解释PEA的抗炎和抗痛觉过敏作用，包括PPAR-δ和PPAR-γ的活化。本研究的目的是仔细研究PPAR-δ和PPAR-γ以及PPAR-α在PEA对与脊髓损伤（SCI）相关的继发性炎症损伤的保护作用中的确切作用。方法通过四层T5至T8椎板切除术对硬脑膜施加血管夹（24 g力）并施加硬膜外麻醉（10 mg / kg，腹膜内1、6小时），通过脊髓压迫诱导脊髓损伤将其注射到野生型小鼠和缺乏PPAR-α（PPAR-αKO）的小鼠体内。为了加深特定PPAR-δ和PPAR-γ拮抗剂逆转PEA效应的能力，在PEA注射前30分钟给小鼠施用GSK0660或GW9662。结果小鼠中PPAR-α的遗传消除加剧了脊髓损伤，而PPARαKO小鼠中PEA诱导的神经保护作用似乎被取消了。脊髓损伤后二十四小时，对脊髓组织进行了免疫组织学和生化研究。我们的结果表明，PPAR-δ和PPAR-γ也介导了PEA诱导的保护作用。尤其是，通过脊髓炎症和组织损伤，中性粒细胞浸润，促炎性细胞因子，诱导型一氧化氮合酶表达和运动功能的程度评估，PEA在PPAR-αKO，经GSK0660治疗或GW9662治疗的小鼠中效果较差。 PEA还能够恢复脊髓组织中的PPAR-δ和PPAR-γ表达。结论：本研究表明PPAR-δ和PPAR-γ也可促进SCI中PEA的抗炎活性。

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