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微复合棕榈酰乙醇酰胺/芦丁通过调节 Nrf2/HO-1 和 NF-kB 通路减少血管损伤。

Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO-1 and NF-kB Pathways.

机构信息

Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, n 31, Messina 98166, Italy.

Department of Biomedical, Dental and Morphological and Functional Imaging University of Messina, Via Consolare Valeria, 98125 Messina, Italy.

出版信息

Curr Med Chem. 2021;28(30):6287-6302. doi: 10.2174/0929867328666210329120213.

Abstract

BACKGROUND

Vascular remodeling processes induced by acute and chronic injuries are characterized by inflammation and oxidative stress. In arteriosclerosis, atherosclerosis, and restenosis, the progression of neointimal hyperplasia is a key event of vascular damage.

OBJECTIVE

Our study was aimed to investigate the inflammation and oxidative stress development during vascular impairment and the potential efficacy of treatment of new micro composite N-palmitoylethanolamine/Rutin at a ratio of 1:1 (PEA/RUT). The anti-inflammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has important pharmacological actions, including antioxidant and vasoprotective.

METHODS

As a model of vascular injury, we used the complete ligature of the left carotid artery for fourteen days and administered PEA/RUT at the dose of 10 mg/Kg.

RESULTS

This study demonstrated that after fourteen days of carotid ligation, there is a substantial structural change in the vessel morphology, with inflammatory cell infiltration and reactive oxygen species production. PEA/RUT administration reduced change in vascular morphology, cytokines like monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules expression like intercellular adhesion molecules-1 (ICAM-1), proinflammatory cytokines production (IL-1 β, IL-6 and TNF- α), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway).

CONCLUSION

Our data clearly demonstrate the beneficial effect of PEA/RUT administration in reducing inflammation, oxidative stress, and vascular damage.

摘要

背景

急性和慢性损伤诱导的血管重塑过程的特征是炎症和氧化应激。在动脉粥样硬化、动脉粥样硬化和再狭窄中,新生内膜增生的进展是血管损伤的关键事件。

目的

我们的研究旨在探讨血管损伤过程中的炎症和氧化应激发展,以及新的微复合 N-棕榈酰乙醇胺/芦丁(PEA/RUT)比例为 1:1 的治疗的潜在疗效。棕榈酰乙醇胺(PEA)的抗炎作用是众所周知的。芦丁具有重要的药理作用,包括抗氧化和血管保护作用。

方法

作为血管损伤的模型,我们使用左颈总动脉完全结扎 14 天,并给予 PEA/RUT 剂量为 10mg/kg。

结果

本研究表明,在颈总动脉结扎 14 天后,血管形态发生了实质性的结构变化,伴有炎症细胞浸润和活性氧的产生。PEA/RUT 给药减少了血管形态的变化,减少了单核细胞趋化蛋白-1(MCP-1)等细胞因子和细胞间黏附分子-1(ICAM-1)等黏附分子的表达,减少了促炎细胞因子(IL-1β、IL-6 和 TNF-α)的产生,减少了氧化和硝化应激(硝基酪氨酸和 PARP 表达和 NRF2 途径)。

结论

我们的数据清楚地表明,PEA/RUT 给药在减轻炎症、氧化应激和血管损伤方面具有有益的效果。

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