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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2016年第4期

页码:

401-404

栏目:

基础研究

出版日期:

2016-04-01

文章信息/Info

Title:

Effects and mechanism of glucagon-like peptid-1 on atherosclerosis

作者:

张东伟¹; 康艳霞²

（第四军医大学：1.西京医院心脏内科，陕西 西安 710032，2.唐都医院肿瘤科，陕西 西安 710038）

Author(s):

ZHANG Dong-wei¹;  KANG Yan-xia²

(1.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China, 2.Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, China)

关键词:

动脉粥样硬化; GLP-1; ICAM-1; VCAM-1; E-selectin

Keywords:

atherosclerosis;  GLP-1;  ICAM-1;  VCAM-1;  E-selectin

分类号:

R711.75

DOI:

-

文献标识码:

A

摘要:

目的 探索胰高血糖素样肽（GLP）-1对氧化低密度脂蛋白（ox-LDL）诱导的人脐静脉内皮细胞（HUVECs）损伤的作用及机制。方法 将体外培养HUVECs分为对照组（无处理）和GLP-1预处理组（分别给予0、2.5、5和10 nmol/L GLP-1预处理24 h后，再以100 μg/ml ox-LDL氧化24 h）。应用MTT法检测细胞生存率，评估GLP-1在ox-LDL诱导HUVECs损伤中的作用；应用免疫荧光技术评估GLP-1在ox-LDL诱导单核细胞对HUVECs的黏附的影响；应用ELISA法检测HUVECs在接受ox-LDL和GLP-1处理后E-选择素，细胞间黏附分子（ICAM）-1、血管细胞黏附分子（VCAM）-1的分泌，并应用RT-PCR法检测E-选择素、ICAM-1、VCAM-1基因表达。结果 MTT试验显示（2.5、5和10 μmol/L）的GLP-1均可降低ox-LDL对HUVECs的杀伤作用，保护作用与浓度呈正相关（P<0.05）；免疫荧光检测结果显示，GLP-1可以降低单核细胞对ox-LDL损伤HUVECs的黏附作用，且和浓度呈正相关（P<0.05）。GLP-1处理后的ICAM-1、VCAM-1及E-选择素的表达和分泌均有显著下降（均有P<0.05）。结论 GLP-1可能通过对抗HUVECs氧化损伤，下调ICAM-1、VCAM-1和E-选择素的表达与分泌，减少单核细胞趋化和黏附，发挥抗动脉粥样硬化作用。

Abstract:

AIM To investigate the effects and mechanism of glucagon-like peptid-1 (GLP-1) against human umbilical vein endothelial cells (HUVECs) injured by oxidized low-density lipoprotein (ox-LDL). METHODSCultured HUVECs were divided into control group (without treatment) and GLP-1 pretreatment groups (pretreated with 0, 2.5, 5, 10 nmol/L GLP-1 for 24 h and then added to 100 μg/ml ox-LDL for 24 h). Effects of GLP-1 on the activity of HUVECs induced by oxidized low-density lipoprotein (ox-LDL) were detected by MTT assay and the effects of GLP-1 on the adhesion of monocytes with HUVECs induced by ox-LDL were studied. Secretions of E-selectin, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) by HUVECs were measured by ELISA and mRNA levels of ICAM-1, VCAM-1 and E-selectin of HUVECs were analyzed by real time RT-PCR. RESULTSMTT results indicated that GLP-1 (2.5, 5, 10 μmol/L) could inhibit HUVECs injury induced by ox-LDL in a concentration-dependent manner (P<0.05). Adhesion of monocytes with HUVECs induced by ox-LDL was inhibited by GLP-1 in a concentration-dependent manner (P<0.05). Levels of ICAM-1, VCAM-1 and E-selectin in GLP-1 groups were significantly decreased compared with those in ox-LDL-simulated group (P<0.05). mRNA expressions of ICAM-1, VCAM-1 and E-selectin in GLP-1 groups were also significantly downregulated compared with those in ox-LDL-simulated group (P<0.05). CONCLUSIONGLP-1 can prevent atherosclerotic lesion. The mechanisms may be that GLP-1 can defend against oxidation damage to HUVECs, inhibit adhesion of monocytes to HUVECs and reduce the secretion and expression of adhesion molecules including ICAM-1, VCAM-1 and E-selectin.

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备注/Memo

备注/Memo:

收稿日期：2015-08-12.
通讯作者：康艳霞，主治医师，主要从事心血管病介入诊治研究 Email:Kyx-522@163.com
作者简介：张东伟,主治医师，硕士 Email：zhdwuu@163.com

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更新日期/Last Update: 2016-04-01