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橄榄苦苷对大鼠肾缺血再灌注损伤诱导的氧化应激、炎症和细胞凋亡的影响。

Effect of oleuropein on oxidative stress, inflammation and apoptosis induced by ischemia-reperfusion injury in rat kidney.

机构信息

Laboratoire de Génome Humain et Maladies Multifactorielles (LR12ES07), Faculté de Pharmacie de Monastir, Université de Monastir, Tunisia.

Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, équipe: Chimie Médicinale et Produits Naturels (LR11ES39), Faculté des Sciences de Monastir, Université de Monastir, Monastir, Tunisia.

出版信息

Life Sci. 2020 Aug 15;255:117833. doi: 10.1016/j.lfs.2020.117833. Epub 2020 May 22.

Abstract

AIMS

This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism.

MAIN METHODS

Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot.

KEY FINDINGS

Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys.

SIGNIFICANCE

In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties.

摘要

目的

本研究旨在评估橄榄叶中主要的酚类化合物橄榄苦苷(OLE)对肾缺血再灌注损伤(IRI)的影响,并探讨其潜在的保护机制。

方法

大鼠肾脏缺血 60 分钟后再灌注 120 分钟。OLE 在缺血前 48 小时、24 小时和 30 分钟,以 10、50 和 100mg/kg 体重的剂量口服给予。评估血浆中肌酐、尿素、尿酸浓度和乳酸脱氢酶(LDH)活性。还评估了氧化应激和炎症参数。使用 Western blot 评估肾组织中 AMP 激活蛋白激酶(p-AMPK)、内皮型一氧化氮合酶(eNOS)、丝裂原活化蛋白激酶(MAPK)、炎症蛋白和凋亡蛋白的表达。

主要发现

我们的结果表明,50mg/kg 的 OLE 通过显著降低血浆肌酐、尿素、尿酸浓度和 LDH 活性减轻了肾 IRI。同时,OLE 增加了抗氧化能力。此外,OLE 降低了 CRP 水平和环氧化酶 2(COX-2)的表达。最后,OLE 增强了 AMPK 的磷酸化和 eNOS 的表达,而细胞凋亡相关的 MAPK 和 cleaved caspase-3 则在缺血肾脏中受到抑制。

意义

总之,本研究表明,OLE 可作为治疗剂,通过其抗氧化、抗炎和抗凋亡特性来减少 IRI。

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