胰高血糖素样肽-1（GLP-1）是肠道L细胞分泌的一种多功能肽类激素，在调节葡萄糖稳态中发挥重要作用,但其对糖尿病大血管病变影响的相关研究甚少。我们的前期研究发现，高糖可引起内皮细胞氧化应激水平改变，GLP-1对内皮细胞氧化应激及凋亡具有改善作用，NOX4是内皮细胞产生活性氧的重要酶，GLP-1是否及如何影响NOX4表达及活性尚无明确报道。为此，我们提出假说：GLP-1可通过调节细胞内NOX4的表达与活性来改善糖脂毒性诱导的氧化应激及内皮细胞凋亡水平。我们拟通过人脐静脉内皮细胞和糖尿病大鼠模型，研究GLP-1影响活性氧产生的分子机制，并探讨其对人脐静脉内皮细胞、糖尿病大鼠模型的糖脂毒性氧化损伤的保护作用，明确GLP-1干预氧化应激改善内皮细胞功能紊乱，减少细胞凋亡的调控机制。本研究将从GLP-1这个新视点为2型糖尿病血管并发症的防治提供新的思路。

Endothelial lesion play a pivotal role in the early pathophysiology of diabetic vascular disorders. The glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone secreted by intestinal epithelial endocrine L-cells ,it plays an important role in the regulation of glucose homeostasis. Our previous study found that high glucose could induce oxidative stress in human umbilical vein endothelial cells (HUVECs).And GLP-1 reduced oxidative stress and apoptosis in the endothelial cells through the regulation on the generation of reactive oxygen important enzyme NOX4,but the machanism has not been elucidated.so we propose that GLP-1 attenuates glucose and lipid toxicity induced oxidative stress and apoptosis of endothelial cells by regulating the expression and activity of NOX4. We will examine the protective effects of GLP-1 on endothlial injury in HUVECs and rat model of diabetes analyze the role of GLP-1 on endothelial cell injury of glucolipotoxicity and discuss themolecular machanism of GLP-1's effcet on the production of ROS. . This study will explore the role of GLP-1 in the vascular complications of type 2 diabetes prevention and treatment from a new perspective.