BACKGROUND High glucose affects the function of endothelial cells by increasing oxidative stress. Studies have found that exendin-4 can improve wound healing in diabetic mice and mice with normal blood glucose. However, the mechanism of exendin-4 in endothelial progenitor cells under high-glucose condition has not been fully elucidated. METHODS Diabetic mouse models were established to investigate the effects of exendin-4 on endothelial progenitor cells in diabetic mice. Serum superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by WST-8 and thiobarbituric acid (TBA) colorimetry, respectively. Cell viability, apoptosis and reactive oxygen species (ROS) were detected by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry. Gene and protein expressions were determined by Quantitative reverse transcription PCR (qRT-PCR) assay and Western blot (WB). RESULTS The results showed that in diabetic mice, exendin-4 did not affect blood glucose or body weight, moreover, it improved aortic diastolic function, increased SOD activity and down-regulated malondialdehyde (MDA) level in the mice. In addition, exendin-4 also increased endothelial progenitor cell (EPCs) viability and reduced cell apoptosis through inhibiting p38 MAPK pathway and reducing endoplasmic reticulum stress and ROS. CONCLUSION Exndin-4 can alleviate diabetes-caused damage to mice, moreover, it reduced endoplasmic reticulum stress and ROS through inhibiting p38 MAPK pathway in MPCs cells under high-glucose condition, thus increasing cell viability and reducing cell apoptosis.

中文翻译：

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Exendin-4调节内质网应激，以保护内皮祖细胞免受高糖损害。

背景技术高葡萄糖通过增加氧化应激影响内皮细胞的功能。研究发现，exendin-4可以改善糖尿病小鼠和血糖正常的小鼠的伤口愈合。但是，尚未充分阐明在高葡萄糖条件下内皮祖细胞中exendin-4的机制。方法建立糖尿病小鼠模型，研究exendin-4对糖尿病小鼠内皮祖细胞的影响。血清超氧化物歧化酶（SOD）和丙二醛（MDA）分别通过WST-8和硫代巴比妥酸（TBA）比色法测定。通过3-（4,5-二甲基噻唑-2-基）-2、5-二苯基溴化四氮唑（MTT）和流式细胞仪检测细胞活力，凋亡和活性氧（ROS）。通过定量逆转录PCR（qRT-PCR）分析和蛋白质印迹（WB）确定基因和蛋白质表达。结果结果表明，在糖尿病小鼠中，exendin-4不会影响血糖或体重，而且，它改善了小鼠的主动脉舒张功能，增加了SOD活性并下调了丙二醛（MDA）水平。此外，exendin-4还通过抑制p38 MAPK途径并减少内质网应激和ROS，提高了内皮祖细胞（EPC）的活力并减少了细胞凋亡。结论Exndin-4可以减轻糖尿病引起的小鼠损伤，并且通过抑制高糖条件下MPCs细胞中的p38 MAPK途径，减轻内质网应激和ROS，从而增加细胞活力并减少细胞凋亡。