【摘要】 目的 探讨胰升血糖素样肽-1(GLP-1)类似物利拉鲁肽对体外培养的人脐静脉内皮细胞(HUVECs)胰岛素受体底物-1(IRS-1)、一氧化氮合酶(eNOS)和磷酸化eNOS(p-eNOS)表达的影响。 方法 以含有5.5 mmol/L葡萄糖的DMEM培养基体外培养HUVECs，将上述细胞分为10组，各组中均加入3 nmol/L的利拉鲁肽注射液干预，分别于第0、10、15、30、45、60、90、120、150、180 min提取细胞，以Western blot检测各组细胞IRS-1、eNOS及p-eNOS表达情况。 结果 利拉鲁肽干预HUVECs不同时间后，各组细胞表达IRS-1和p-eNOS有所不同，0、10、15 min细胞p-eNOS表达比较，差异无统计学意义(P>0.05)。从第30 min开始，p-eNOS表达逐渐增加，至第150 min达峰，随之p-eNOS表达量开始下降(P<0.05);IRS-1表达趋势与p-eNOS相似，也具有利拉鲁肽时间依赖性，且作用高峰亦为150 min(P<0.05);而各时间点eNOS表达比较，差异均无统计学意义(P>0.05)。 结论 GLP-1类似物利拉鲁肽呈时间依赖性的促进正糖培养的HUVECs IRS-1及p-eNOS的表达，其作用高峰为第150 min，而对eNOS的表达未观察到促进作用。

　　【关键词】 胰升血糖素样肽-1;利拉鲁肽;人脐静脉内皮细胞;胰岛素受体底物1;内皮细胞一氧化氮合酶

　　The effect of liraglutide on eNOS and IRS-1 in human umbilical vein endothelial cells Department of Endocrinology, Wuhan General Hospital of Guangzhou Military Area Command , Wuhan 430070, China

　　【Abstract】 Objective To explore the effects of glucagon like peptide-1 (GLP-1) analogue liraglutide on endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS) and insulin receptor substrates-1 (IRS-1) activation in human umbilical vein endothelial cells(HUVECs) in vitro. Methods HUVECs were cultured in DMEM containing 5.5 mmol/L glucose, then divided into 10 groups. HUVECs of each group were incubated with liraglutide (3 nmol/L), after incubation，cells were extracted in the 0th, 10th, 15th, 30th, 45th, 60th, 90th, 120th, 150th, 180th minutes’respectively. The expression levels of eNOS, p-eNOS and IRS-1 at each point were measured by Western blot. Results There were no significance of p-eNOS levels in 0th, 10th, 15th minutes(P>0.05). However, p-eNOS levels were observed to increased in 30th minute and reached a maximum in 150th minute(P<0.05),and then present a descent trend. IRS-1 activity, followed a similar trend of p-eNOS in a time-dependent manner of liraglutide and peaked in 150th minute. Levels of eNOS had no difference at different time points (P>0.05). Conclutions Liraglutide showed a time-dependent manner to promote the expressions of p-eNOS and IRS-1 in euglycemic cultured HUVECs with peak effect time in 150th minute.However, there was no effect of liralutide on the expressions of eNOS.

　　【Key words】 Glucagon like peptide-1(GLP-1);Liraglutide;Human umbilical vein endothelial cells (HUVECs);Insulin receptor substrates-1 (IRS-1);Endothelial nitric oxide synthase(eNOS)