胰高血糖素样肽-1（GLP-1）可保护血管内皮细胞免受晚期糖基化终产物（AGEs）诱导的细胞凋亡。

BACKGROUND

The peptide glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal L cells in response to food intake. GLP-1 has been proposed as the basis of emerging therapy for patients with type 2 diabetes. However, the effects of GLP-1 on vascular injury in diabetes have not been identified. Advanced glycation end products (AGEs) induce endothelial cell apoptosis and have been implicated in the process of vascular complications from diabetes.

MATERIAL/METHODS: The aim of this work was to investigate whether and how GLP-1 protects endothelial cells from apoptosis induced by AGEs. Human umbilical vein endothelial cells (HUVECs) were treated with AGEs (200 µg/mL) for 48 h in the presence or absence of GLP-1. Cell morphology, viability, apoptosis, ratio of Bcl-2 protein to Bax protein, cytochrome c release, and activity of caspase-9 and -3 were determined.

RESULTS

Treatment of cells with AGEs led to cell morphology changes and decreased cell viability, resulting in apoptosis. GLP-1 alone increased cell viability in a concentration-dependent manner. GLP-1 partially inhibited AGEs-induced apoptosis in HUVECs. GLP-1 increased Bcl-2/Bax ratio, reduced cytochrome c levels in the cytoplasm, and reduced the activity of caspase-9 and -3 in AGEs-treated HUVECs.

CONCLUSIONS

AGEs induces apoptosis via the mitochondrion-cytochrome c-caspase protease pathway, and GLP-1 protects endothelial cells by interfering with this mechanism. GLP-1 may represent an anti-apoptotic agent in the treatment of vascular complications arising from diabetes.

背景

肽类激素胰高血糖素样肽-1（GLP-1）是一种在进食后由肠道 L 细胞分泌的激素。GLP-1 已被提议作为治疗 2 型糖尿病患者的新兴疗法的基础。然而，GLP-1 对糖尿病血管损伤的影响尚未确定。糖基化终产物（AGEs）诱导内皮细胞凋亡，并与糖尿病血管并发症的发生过程有关。

材料/方法：本研究旨在探讨 GLP-1 是否以及如何保护内皮细胞免受 AGEs 诱导的凋亡。将人脐静脉内皮细胞（HUVEC）用 AGEs（200μg/ml）处理 48 小时，同时存在或不存在 GLP-1。测定细胞形态、活力、凋亡、Bcl-2 蛋白与 Bax 蛋白的比值、细胞色素 c 释放和 caspase-9、caspase-3 的活性。

结果

用 AGEs 处理细胞导致细胞形态改变和细胞活力下降，从而导致细胞凋亡。GLP-1 以浓度依赖的方式单独增加细胞活力。GLP-1 部分抑制 HUVECs 中 AGEs 诱导的细胞凋亡。GLP-1 增加了 Bcl-2/Bax 比值，减少了细胞质中细胞色素 c 的水平，并降低了 AGEs 处理的 HUVECs 中 caspase-9 和 caspase-3 的活性。