Department of Pharmacology, Medical Faculty, Akdeniz University, 07070, Antalya, Turkey.
Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070, Antalya, Turkey.
Aging Clin Exp Res. 2019 Mar;31(3):331-338. doi: 10.1007/s40520-018-0986-x. Epub 2018 Jun 27.
The cardiovascular benefits of resveratrol (RSV) have been well established by previous experimental and clinical studies. The aim of this study was to investigate the effectiveness of RSV administration on the impaired endothelial function induced by methylglyoxal (MGO), and to elucidate the role of endothelial nitric oxide synthase (eNOS) on its protective effect.
Aged Wistar rats (80 weeks old, n = 15) were used in this study. The thoracic aorta was isolated and cut into rings for organ culture. Aortic segments of rats were incubated with MGO (420 µM) in the presence or absence of RSV (30 µM) for 4 h (short-term) or 24 h (long-term). Isometric tension studies were performed by an isolated organ bath in response to acetylcholine (ACh, an endothelium-dependent vasodilator) and sodium nitroprusside (SNP, an endothelium-independent vasodilator). Beside, expressions of eNOS and phospho-eNOS (p-eNOS) (Ser 1177) in thoracic aorta rings were evaluated by immunohistochemistry.
Both short-term and long-term MGO incubation significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. In addition, eNOS and p-eNOS expressions decreased significantly in arteries incubated with MGO. The impaired endothelial reactivity as well as decreased expressions of eNOS and p-eNOS in MGO-incubated vessels were significantly improved by RSV treatment.
Endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by MGO administration, and RSV may improve vascular endothelial function. The protective effect of RSV against MGO-induced endothelial dysfunction seems to be via increased eNOS expression and activity.
已有多项实验和临床研究证实白藜芦醇（RSV）对心血管有益。本研究旨在探讨 RSV 对甲基乙二醛（MGO）诱导的内皮功能障碍的作用，并阐明内皮型一氧化氮合酶（eNOS）在其保护作用中的作用。
本研究使用 80 周龄 Wistar 大鼠。分离胸主动脉并切成环用于器官培养。将大鼠主动脉段在存在或不存在 RSV（30 μM）的情况下用 MGO（420 μM）孵育 4 小时（短期）或 24 小时（长期）。通过离体器官浴进行等长张力研究，以响应乙酰胆碱（ACh，一种内皮依赖性血管舒张剂）和硝普钠（SNP，一种内皮非依赖性血管舒张剂）。此外，通过免疫组织化学评估胸主动脉环中 eNOS 和磷酸化 eNOS（Ser 1177）的表达。
短期和长期 MGO 孵育均显著抑制 ACh 诱导的舒张反应，而 SNP 引起的舒张反应无显著改变。此外，MGO 孵育的动脉中 eNOS 和 p-eNOS 的表达明显降低。RSV 处理可显著改善 MGO 孵育血管内皮反应性以及 eNOS 和 p-eNOS 的表达降低。
MGO 给药显著抑制胸主动脉内皮依赖性血管舒张，RSV 可能改善血管内皮功能。RSV 对 MGO 诱导的内皮功能障碍的保护作用似乎是通过增加 eNOS 的表达和活性实现的。
