Wiciński Michał, Malinowski Bartosz, Węclewicz Mateusz M, Grześk Elżbieta, Grześk Grzegorz
Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-090 Bydgoszcz, Poland.
Exp Ther Med. 2017 May;13(5):2071-2078. doi: 10.3892/etm.2017.4180. Epub 2017 Mar 2.
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.
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。