沙格列汀对稳定性冠心病患者外周血内皮祖细胞功能的影响  

The Effects of Saxagliptin on Endothelial Progenitor Cell Function in Patients with Stable Coronary Heart Disease

作　　者：胡静菊 马列[3] 李银萍[3] 刘志军[3] 李溪[3] 徐清斌[3] 杨志伟[1] 

机构地区：[1]宁夏医科大学基础医学院病原生物学与免疫学系,银川750004 [2]宁夏中卫市人民医院,中卫755000 [3]宁夏医科大学总医院心脑血管病医院心内科,银川750002

出　　处：《宁夏医科大学学报》2017年第4期415-419,F0002,共6页Journal of Ningxia Medical University

摘　　要：目的探讨沙格列汀对稳定冠心病患者内皮祖细胞(endothelial progenitor cell,EPCs)功能的影响。方法提取经冠脉造影证实的稳定性冠心病患者外周血EPCs,激光共聚焦显微镜观察Dil-ac-LDL和FITC-UEA-I双染色阳性细胞,鉴定正在分化的EPCs。使用不同浓度沙格列汀(0、5、10、20和40μmol·L^(-1))进行干预,MTT检测内皮祖细胞增殖能力,并观察沙格列汀影响内皮祖细胞增殖能力的时间依赖关系(0、12、24、36和48h)。Transwell小室试验观察内皮祖细胞的迁移能力。蛋白印迹检测内皮祖细胞磷酸化一氧化氮合成酶(p-eNOS)和一氧化氮合成酶(eNOS)的表达。结果沙格列汀明显增强稳定性冠心病患者EPCs增殖能力,以20μmol·L^(-1)浓度作用最为显著(P<0.05),36h达到作用高峰,但48h后增殖能力下降;而且沙格列汀明显增加EPCs的迁移能力(P<0.05),以40μmol·L^(-1)最为显著,且20和40μmol·L^(-1)沙格列汀p-eNOS和eNOS的表达均上调(P均<0.05)。结论沙格列汀可能通过增强内皮祖细胞迁移和增殖能力,上调p-eNOS和eNOS促进一氧化氮(NO)产生而发挥心血管保护作用。Objective To explore the effects of Saxagliptin on endothelial progenitor cell function in patients with stable coronary heart disease. Methods Endothelial Progenitor Cells（EPCs） were isolated from the peripheral blood in patients with stable coronary heart disease diagnosed by coronary angiography and characterized as adherent cells double positive for Di-LDL uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope.After challenged with different concentrations of Saxagliptin（0,5,10,20,40μmol·L^-1）,the proliferation of EPCs and time dependent manner（0,12,24,36,48h）was detected by MTT. Furthermore,the migration of EPCs was assessed by transwell assay. Finally,the expression of e NOS and p-eNOS（phospho-eNOS）of EPCs was examined by western blot. Results Saxagliptin could significantly improve the proliferation of EPCS especially at the concentration of 20μmol·L^-1（P〈0.05）.Furthermore,EPCs showed a proliferation peak at 36 h and decreased at 48 h. In addition,we found Saxagliptin could stimulate the proliferation of EPCs with a peak at the concentrations of 40μmol·L^-1and could upregulate the expression of p-eNOS and eNOS（P〈0.05）. Conclusion The enhanced migration and proliferation of EPCS and upregulated the expression of p-eNOS and eNOS may be responsible for the favorable role of Saxagliptinin cardiovascular protection.

关 键 词：沙格列汀 内皮祖细胞 增殖 迁移 内皮型一氧化氮合成酶 

分 类 号：R541.4[医药卫生—心血管疾病]