GLP-1对高糖诱导内皮细胞损伤的保护作用及分子机制研究

The protective effect and molecular mechanism of GLP-1 on the high glucose-induced endothelial cell injury

目的:研究胰高血糖素样肽-1(GLP-1)对高糖诱导内皮细胞损伤的保护作用及分子机制。方法:培养内皮细胞HUVECs并分为三组,对照组用不含血清的低糖培养基处理、高糖组用含有40mmol/L葡萄糖的无血清培养基处理、GLP-1组用含有10mmol/L GLP-1及40mmol/L葡萄糖的无血清培养基处理。处理后24小时,测定细胞中凋亡基因、自噬基因的表达量以及氧化应激产物、抗氧化物的含量。结果:高糖组细胞中JAK2、STAT3、Bax、Caspase-9、Caspase-3、Nrf2、NQO1、HO1、GSH-Px的mRNA表达量以及ROS、gp91phox、MDA、ox-LDL的含量显著高于对照组,STSQM1、Atg-5、LC-3的mRNA表达量显著低于对照组;GLP-1组细胞中JAK2、STAT3、Bax、Caspase-9、Caspase-3的mRNA表达量以及ROS、gp91phox、MDA、ox-LDL的含量均显著低于高糖组,Nrf2、NQO1、HO1、GSH-Px、STSQM1、Atg-5、LC-3的mRNA表达量显著高于高糖组。结论:GLP-1能够通过抑制凋亡、减轻氧化应激、增强细胞自噬的途径来减轻高糖诱导的内皮细胞损伤。

Objective:To study the protective effect and molecular mechanism of glucagon-like peptide-1(GLP-1)on the high glucose-induced endothelial cell injury.Methods:Endothelial cells HUVECs were cultured and divided into three groups,control group were treated with serum-free low-glucose culture medium,high glucose group were treated with serumfree culture medium containing 40 mmol/L glucose and GLP-1 group were treated with serum-free culture medium containing10 mmol/L GLP-1 and 40 mmol/L glucose.24 hours after treatment,the expression of apoptosis genes and autophagy genes as well as the levels of oxidative stress products and antioxidants were measured.Results:JAK2,STAT3,Bax,Caspase-9,Caspase-3,Nrf2,NQO1,HO1 and GSH-Px mRNA expression as well as ROS,gp91 phox,MDA and ox-LDL levels in high glucose group of cells were significantly higher than those in control group while STSQM1,Atg-5 and LC-3 mRNA expression were significantly lower than those of control group;JAK2,STAT3,Bax,Caspase-9 and Caspase-3 mRNA expression as well as ROS,gp91 phox,MDA and ox-LDL levels in GLP-1 group of cells were significantly lower than those in high glucose group while Nrf2,NQO1,HO1,GSH-Px,STSQM1,Atg-5 and LC-3 mRNA expression were significantly higher than those in high glucose group.Conclusion:GLP-1 can reduce the high glucose-induced endothelial cell injury by inhibiting apoptosis,reducing oxidative stress and enhancing autophagy.