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首页> 外文期刊>Genes and Nutrition >Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway
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Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

机译：白藜芦醇通过VEGF / KDR途径改善了由小窝介导的高糖诱导的通透性

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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.
机译：高血糖引起的内皮细胞通透性过高是动脉粥样硬化发展的第一步，这是糖尿病中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）（一种从中药虎杖中提取的生物活性成分）对体外渗透性的影响及其涉及的分子机制。通过透过单层内皮细胞​​（EC）渗透的异硫氰酸荧光素（FITC）-葡聚糖的流出评估渗透率。 mRNA水平，蛋白质表达和分泌分别通过实时定量PCR，蛋白质印迹和ELISA进行测量。在暴露于高葡萄糖的单层EC中观察到通透性增加和Caveolin-1（cav-1）表达增加。白藜芦醇治疗以剂量依赖的方式减轻了高糖诱导的cav-1的通透性和过表达。 β-环糊精是小窝的结构抑制剂，可降低高葡萄糖引起的通透性过高。白藜芦醇还下调了高糖诱导的血管内皮生长因子（VEGF）和激酶插入域受体（KDR或VEGF受体2）的表达增加。通过使用SU5416（一种选择性的KDR抑制剂）抑制VEGF / KDR途径，可减轻高葡萄糖诱导的过渗透性和cav-1过表达。以上结果表明，RSV改善了通过VEGF / KDR途径由高糖诱导的小窝介导的通透性。

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