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, M. Curie 9, 85-090 Bydgoszcz, Poland.
Biomed Res Int. 2017;2017:9202954. doi: 10.1155/2017/9202954. Epub 2017 Feb 5.
Resveratrol is a polyphenol that presents both antineuroinflammatory properties and the ability to interact with NOS-3, what contributes to vasorelaxation. Brain-derived neurotrophic factor (BNDF), a molecule associated with neuroprotection in many neurodegenerative disorders, is considered as an important element of maintaining stable cerebral blood flow. Vascular smooth muscle cells (VSMCs) are considered to be an important element in the pathogenesis of neurodegeneration and a potential preventative target by agents which reduce the contractility of the vessels. Our main objectives were to define the relationship between serum and long-term oral resveratrol administration in the rat model, as well as to assess the effect of resveratrol on phenylephrine- (PHE-) induced contraction of vascular smooth muscle cells (VSMCs). Moreover, we attempt to define the dependence of contraction mechanisms on endothelial NO synthase. Experiments were performed on Wistar rats ( = 17) pretreated with resveratrol (4 weeks; 10 mg/kg ) or placebo. Serum BDNF levels were quantified after 2 and 4 weeks of treatment with ELISA. Contraction force was measured on isolated and perfused tail arteries as the increase of perfusion pressure with a constant flow. Values of serum BNDF in week 0 were 1.18 ± 0.12 ng/mL (treated) and 1.17 ± 0.13 ng/mL (control) ( = ns). After 2 weeks of treatment, BDNF in the treatment group was higher than in controls, 1.52 ± 0.23 ng/mL and 1.24 ± 0.13 ng/mL, respectively. ( = 0.02) Following 4 weeks of treatment, BDNF values were higher in the resveratrol group compared to control 1.64 ± 0.31 ng/mL and 1.32 ± 0.26 ng/mL, respectively ( = 0.031). EC values obtained for PHE in resveratrol pretreated arteries were significantly higher than controls (5.33 ± 1.7 × 10M/L versus 4.53 ± 1.2 × 10M/L, < 0.05). These results show a significant increase in BDNF concentration in the resveratrol pretreated group. The reactivity of resistant arteries was significantly reduced for resveratrol pretreated vessels and this effect was partially NOS-3 independent.
白藜芦醇是一种多酚,具有抗神经炎症特性以及与一氧化氮合酶-3(NOS-3)相互作用的能力,这有助于血管舒张。脑源性神经营养因子(BDNF)是一种在许多神经退行性疾病中与神经保护相关的分子,被认为是维持稳定脑血流量的重要因素。血管平滑肌细胞(VSMC)被认为是神经退行性病变发病机制中的一个重要因素,也是降低血管收缩性的药物潜在的预防靶点。我们的主要目标是确定在大鼠模型中血清与长期口服白藜芦醇之间的关系,以及评估白藜芦醇对去氧肾上腺素(PHE)诱导的血管平滑肌细胞(VSMC)收缩的影响。此外,我们试图确定收缩机制对内皮型一氧化氮合酶的依赖性。实验在预先用白藜芦醇(4周;10mg/kg)或安慰剂处理的Wistar大鼠(n = 17)上进行。用酶联免疫吸附测定法(ELISA)在治疗2周和4周后对血清BDNF水平进行定量。在分离并灌注的尾动脉上测量收缩力,即灌注压力随恒定流量的增加。第0周时血清BDNF值在治疗组为1.18±0.12ng/mL,对照组为1.17±0.13ng/mL(p =无显著差异)。治疗2周后,治疗组的BDNF高于对照组,分别为1.52±0.23ng/mL和1.24±o.13ng/mL(p = 0.02)。治疗4周后,白藜芦醇组的BDNF值高于对照组,分别为1.64±0.31ng/mL和1.32±0.26ng/mL(p = 0.031)。白藜芦醇预处理动脉中PHE的半数有效浓度(EC)值显著高于对照组(5.33±1.7×10⁻⁶M/L对4.53±1.2×10⁻⁶M/L,p < 0.05)。这些结果表明白藜芦醇预处理组中BDNF浓度显著增加。白藜芦醇预处理血管的阻力动脉反应性显著降低,且这种作用部分不依赖于NOS-3。