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白藜芦醇的抗动脉粥样硬化特性:在大鼠模型中,给予白藜芦醇4周与血清中SIRT1、脂联素、S100A8/A9的浓度以及血管平滑肌细胞收缩性相关。

Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model.

作者信息

Wiciński Michał, Malinowski Bartosz, Węclewicz Mateusz M, Grześk Elżbieta, Grześk Grzegorz

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-090 Bydgoszcz, Poland.

出版信息

Exp Ther Med. 2017 May;13(5):2071-2078. doi: 10.3892/etm.2017.4180. Epub 2017 Mar 2.

Abstract

Resveratrol (3, 4', 5-trihydroxy-trans-stilbene) is a natural, non-flavonoid polyphenol that exerts protective properties against atherosclerosis-associated endothelial dysfunction and senescence. The present study aimed to assess the influence of resveratrol on vascular contractility and molecular factors including sirtuin-1 (SIRT1), adiponectin and calprotectin (S100A8/A9) that are considered to be important elements of atherogenesis. A total of 17 male rats were divided into a control and treatment group and administered resveratrol or a placebo. Pharmacometrics were performed on an isolated and perfused tail artery. Serum SIRT1, adiponectin and S100A8/A9 levels were quantified using an ELISA assay. The level of SIRT1 in the control and treatment groups at time 0 was 4.26 and 4.45 ng/ml, respectively. SIRT1 in the control and treatment groups following 2 weeks of treatment was 4.59 and 6.86 ng/ml, respectively (P<0.05) and following 4 weeks of treatment was 4.15 and 6.38 ng/ml, respectively (P<0.05). The level of adiponectin in the control and treatment groups at time 0 was 1.24 and 1.21 ng/ml, respectively. Following 2 weeks of treatment, the level of adiponectin in the control and treatment groups was 1.22 and 1.2 ng/ml, respectively (P>0.05) and following 4 weeks of treatment was 1.26 and 1.58 ng/ml, respectively (P<0.05). The S100A8/A9 level in control and treatment groups at time 0 was 0.39 and 0.33 ng/ml, respectively. The level of S100A8/A9 in control and treatment groups following 2 weeks of treatment was 0.37 and 0.35 ng/ml, respectively (P>0.05) and following 4 weeks of treatment was 0.34 and 0.32 ng/ml, respectively (P>0.05). EC values obtained for phenylephrine in resveratrol-pretreated arteries were significantly higher than controls in the presence and absence of A7-hydrochloride (P<0.05). The results of the present study indicate a significant increase in the concentration of SIRT1 and adiponectin in the resveratrol-pretreated group (P<0.05). S100A8/A9 serum concentrations remained unchanged. Reactivity of resistant arteries was significantly reduced for resveratrol-pretreated vessels and this effect was partially independent of phosphodiesterase (PDE1). Additionally, there was a synergistic interaction observed between resveratrol and the PDE1 inhibitor.

摘要

白藜芦醇(3,4',5-三羟基反式芪)是一种天然的非黄酮类多酚,对动脉粥样硬化相关的内皮功能障碍和衰老具有保护作用。本研究旨在评估白藜芦醇对血管收缩性以及包括沉默调节蛋白-1(SIRT1)、脂联素和钙卫蛋白(S100A8/A9)等分子因子的影响,这些因子被认为是动脉粥样硬化发生的重要因素。总共17只雄性大鼠被分为对照组和治疗组,并分别给予白藜芦醇或安慰剂。对分离并灌注的尾动脉进行药效学测定。使用酶联免疫吸附测定法对血清SIRT1、脂联素和S100A8/A9水平进行定量。在时间0时,对照组和治疗组的SIRT1水平分别为4.26和4.45纳克/毫升。治疗2周后,对照组和治疗组的SIRT1分别为4.59和6.86纳克/毫升(P<0.05),治疗4周后分别为4.15和6.38纳克/毫升(P<0.05)。在时间0时,对照组和治疗组的脂联素水平分别为1.24和1.21纳克/毫升。治疗2周后,对照组和治疗组的脂联素水平分别为1.22和1.2纳克/毫升(P>0.05),治疗4周后分别为1.26和1.58纳克/毫升(P<0.05)。在时间0时,对照组和治疗组的S100A8/A9水平分别为0.39和0.33纳克/毫升。治疗2周后,对照组和治疗组的S100A8/A9水平分别为0.37和0.35纳克/毫升(P>0.05),治疗4周后分别为0.34和0.32纳克/毫升(P>0.05)。在存在和不存在A7-盐酸盐的情况下,白藜芦醇预处理动脉中去氧肾上腺素的EC值显著高于对照组(P<0.05)。本研究结果表明,白藜芦醇预处理组中SIRT1和脂联素的浓度显著增加(P<0.05)。S100A8/A9血清浓度保持不变。白藜芦醇预处理血管的阻力动脉反应性显著降低,且这种作用部分独立于磷酸二酯酶(PDE1)。此外,观察到白藜芦醇与PDE1抑制剂之间存在协同相互作用。

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