Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Endocrinology, Ministry of Health, Beijing Hospital, Beijing, China.
Sci Rep. 2017 Aug 14;7(1):8008. doi: 10.1038/s41598-017-06712-z.
The aim of this work was to evaluate the effects of glucagon-like peptide-1 (GLP-1) on high-glucose-induced oxidative stress and investigate the possible mechanisms underlying this process. We measured reactive oxygen species (ROS) production, cell apoptosis, the expression of NOX4 and its subunits, and p47phox translocation in human umbilical vein endothelial cells (HUVECs). An experimental type 2 diabetes model was induced using streptozotocin in male Sprague-Dawley rats. Fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and free fatty acid (FFA) were measured. Histomorphological analysis of the aorta was performed using hematoxylin-eosin staining. NOX4 and VCAM-1 expression in the aorta was measured. We found that high-glucose-induced ROS production and apoptosis were inhibited by GLP-1 treatment. High glucose caused upregulation of NOX4, p47phox, and Rac-1 and translocation of p47phox but had no effect on the cells pretreated with GLP-1. Furthermore, in the diabetic group, FBG, FINS, TG, TC, and FFA were increased, and NOX4 and VCAM-1 levels were also elevated. However, GLP-1 attenuated all these changes. GLP-1 ameliorated high-glucose-induced oxidative stress by inhibiting NOX4, p47phox, and Rac-1 expression and translocation of p47phox, suggesting its clinical usefulness in diabetic vascular complications.
本研究旨在评估胰高血糖素样肽-1（GLP-1）对高糖诱导的氧化应激的影响，并探讨其潜在机制。我们测量了人脐静脉内皮细胞（HUVEC）中活性氧（ROS）的产生、细胞凋亡、NOX4 及其亚基的表达以及 p47phox 的易位。采用链脲佐菌素诱导雄性 Sprague-Dawley 大鼠建立实验性 2 型糖尿病模型。检测空腹血糖（FBG）、空腹胰岛素（FINS）、总胆固醇（TC）、甘油三酯（TGs）和游离脂肪酸（FFA）。采用苏木精-伊红染色对主动脉进行组织形态学分析。检测主动脉中 NOX4 和 VCAM-1 的表达。我们发现 GLP-1 处理可抑制高糖诱导的 ROS 产生和细胞凋亡。高糖可上调 NOX4、p47phox 和 Rac-1，促进 p47phox 易位，但对 GLP-1 预处理的细胞无影响。此外，在糖尿病组中，FBG、FINS、TG、TC 和 FFA 增加，NOX4 和 VCAM-1 水平也升高。然而，GLP-1 减轻了所有这些变化。GLP-1 通过抑制 NOX4、p47phox 和 Rac-1 的表达和 p47phox 的易位减轻了高糖诱导的氧化应激，表明其在糖尿病血管并发症的临床应用价值。
