The anti-inflammatory effects of palmitoylethanolamide (PEA) on endotoxin-induced uveitis in rats

The anti-inflammatory effects of palmitoylethanolamide (PEA) on endotoxin-induced uveitis in rats
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DOI:
10.1016/j.ejphar.2015.04.025
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发表时间:
2015-08-15
影响因子:
5
通讯作者:
Cuzzocrea, Salvatore
Cuzzocrea, Salvatore
中科院分区:
医学2区
文献类型:
--
作者:
Impellizzeri, Daniela;Ahmad, Akbar;Cuzzocrea, Salvatore

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本研究的目的是研究棕榈酰乙醇酰胺(PEA),一种内源性脂肪酸酰胺,属于n -酰基乙醇胺(NAEs)家族,在大鼠遭受漆膜毒素诱导的葡萄膜炎(EIU)中的作用。雄性大鼠单足注射200 Ltg脂多糖(LPS)诱导ElU。分别于LPS注射前1 h和7 h腹腔注射PEA。另一组动物用载具治疗。给予地塞米松(DEX)作为阳性对照。注射后16 h处死大鼠,收集眼组织进行组织学、免疫组化和western blot分析。虹膜-睫状体组织学检查显示内皮细胞嗜中性粒细胞浸润增多,血管核修饰增多。PEA治疗可减少炎症细胞浸润,改善眼组织的组织学损伤。此外,PEA治疗可降低促炎肿瘤坏死因子(tnf - α)水平、蛋白质外溢和脂质过氧化。免疫组化分析显示,lps注射大鼠细胞内粘附分子(ICAM)-1和硝基酪氨酸呈阳性染色。经PEA处理的ps注射大鼠眼切片中ICAM-1和硝基酪氨酸的染色程度显著降低。western blot检测炎症眼组织诱导型一氧化氮合酶(iNOS)和核因子(np - κ B)的升高。PEA强烈抑制iNOS表达和细胞核NP-kappa B易位。因此,在本研究中,我们证明了PEA降低了ELU大鼠模型的眼部炎症程度。(C) 2015 Elsevier B.V.版权所有
The aim of this study was to investigate the effects of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs), in rats subjected to enclotoxininduced uveitis (EIU). ElU was induced in male rats by a single footpad injection of 200 Ltg lipopolysaccharide (LPS). PEA was administered intraperitoneally at 1 h before and 7 h after injection of LPS. Another group of animals was treated with vehicle. Dexamethasone (DEX) was administered as a positive control. Rats were sacrificed 16 h after injection and the eyes tissues were collected for histology, immunohistochemical and western blot analyses. The histological evaluation of the iris-ciliary body showed an increase of neutrophilic infiltration and nuclear modification of vessel of endothelial cells. PEA treatment decreased the inflammatory cell infiltration and improved histological damage of eye tissues. In addition, PEA treatment reduced pro-inflammatory tumor necrosis factor (TNF-alpha) levels, protein extravasion and lipid peroxidation. Immunohistochemical analysis for intracellular adhesion molecule (ICAM)-1 and nitrotyrosine showed a positive staining from LPS-injected rats. The degree of staining for ICAM-1 and nitrotyrosine was significantly reduced in eye sections from [PS-injected rats treated with PEA. In addition, an increase of inducible nitric oxide synthase (iNOS) and nuclear factor (NP-kappa B) was also evaluated in inflammed ocular tissues by western blot. PEA strongly inhibited iNOS expression and nuclear NP-kappa B translocation. Thus, in this study we demonstrated that PEA reduces the degree of ocular inflammation in a rat model of ELU. (C) 2015 Elsevier B.V. All rights reserved.