Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Genes Nutr. 2013 Mar;8(2):231-9. doi: 10.1007/s12263-012-0319-1. Epub 2012 Sep 16.
Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. β-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.
高血糖引起的血管内皮通透性增加是动脉粥样硬化发生的初始步骤，也是糖尿病最严重的心血管并发症之一。在本研究中，我们研究了白藜芦醇（RSV）对体外通透性的影响及其涉及的分子机制。RSV 是从中药虎杖的根茎中提取的一种生物活性成分，通透性通过荧光素异硫氰酸酯（FITC）-葡聚糖渗透单层内皮细胞（ECs）来评估。通过定量实时 PCR、western blot 和 ELISA 分别测量 mRNA 水平、蛋白表达和分泌。在高葡萄糖暴露的单层 ECs 中观察到通透性增加和窖蛋白-1（cav-1）表达增加。RSV 处理以剂量依赖性方式减轻高葡萄糖诱导的高通透性和 cav-1 过表达。β-环糊精是质膜窖的结构抑制剂，可降低高葡萄糖引起的通透性增加。RSV 还下调了高葡萄糖诱导的血管内皮生长因子（VEGF）和激酶插入结构域受体（KDR，或 VEGF 受体-2）表达的增加。使用选择性 KDR 抑制剂 SU5416 抑制 VEGF/KDR 途径，可减轻高葡萄糖诱导的高通透性和 cav-1 过表达。上述结果表明，RSV 通过 VEGF/KDR 途径改善高葡萄糖诱导的 caveolae 介导的高通透性。
