胰高血糖素样肽-1对高糖诱导人脐静脉内皮细胞凋亡的影响及相关机制  

Effect of GLP-1 on high glucose-induced human umbilical vein endothelial cell apoptosis and mechanism

作　　者：袁小燕[1] 陈科[1] 何红晖[1] 赵立玲[1] 莫朝晖[1] 

机构地区：[1]中南大学湘雅三医院内分泌科,长沙410013

出　　处：《中南大学学报（医学版）》2013年第10期1029-1034,共6页Journal of Central South University ：Medical Science

摘　　要：目的:探讨胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)对高糖诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)凋亡的影响及相关机制。方法:HUVECs加入不同处理因素后分组,分别培养48 h后,MTT检测细胞活力;流式细胞仪检测细胞早期凋亡率;Western印迹测定细胞p-Akt,p-eNOS水平;NO试剂盒检测NO浓度。结果:高糖(33 mmol/L)培养48 h后HUVECs细胞活力下降(P<0.05),细胞凋亡率增加(P<0.01),细胞p-Akt,p-eNOS,NO水平均下降(P<0.05);高糖条件下加入GLP-1(3 nmol/L)培养48 h,与高糖组相比较,HUVECs细胞活力增加(P<0.01),细胞凋亡率减少(P<0.05),细胞p-Akt,p-eNOS,NO水平均增加(P<0.05);PI3K抑制剂wortmannine(100nmol/L)可以阻断GLP-1的抗凋亡作用及其对p-Akt蛋白、p-eNOS蛋白及NO水平的影响;eNOS抑制剂L-NAME(100μmol/L)仅能阻断GLP-1的抗凋亡作用及对NO水平的影响,不影响p-Akt蛋白的表达。结论:GLP-1可改善高糖诱导的HUVECs凋亡,该抗凋亡作用可能与PI3K/Akt/eNOS通路的上调相关。Objective： To investigate the effects of glucagon-like peptide- 1 （GLP- 1） on high glucose-induced apoptosis of human umbilical vein endothelial cells （HUVECs） and the mechanism involved. Methods： HUVECs were cultured under varying conditions for 48 h, and the cell viability was spectrophotometrically measured by MTT assay. Flow cytometry detected the ratio of cell apoptosis. Western blot detected the protein levels of p-Akt and p-eNOS, while NO assay kit detected the NO concentration. Results： Treatment of high glucose （33 mmol/L） for 48 h significantly decreased the HUVECs viability and induced the apoptosis of HUVECs, concomitant with decreased Akt and eNOSphosphorylation leves and subsequent NO production. Treatment with GLP-1 （3 nmol/L） for 48 h in the high glucose group increased the HUVECs viability （P〈0.01）, decreased the ratio of HUVECs early apoptosis （P〈0.05）, ameliorated the reduced protein levels ofp-Akt and p-eNOS caused by high glucose, and increased the NO production （P〈0.05）. The anti-apoptotic effect and the increased NO production of GLP-lwere inhibited by PI3K inhibitor wortmannine （100 umol/L） or eNOS inhibitor L-NAME （100 umol/L）. The effect on p-Akt, p-eNOS of GLP-1 was inhibited by wortmannine （100 umol/L） while L-NAME （ 100 umol/L） did not have any influence on the expression ofp-Akt.

关 键 词：胰高血糖素样肽-1 人脐静脉内皮细胞 高糖 凋亡 

分 类 号：R587.2[医药卫生—内分泌]