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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5.5mmol/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3nmol/L的利拉鲁肽注射液干预,分别于第0、10、15、30、45、60、90、120、150、180min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、15min细胞p-eNOS表达比较,差异无统计学意义(P>0.05)。从第30min开始,p-eNOS表达逐渐增加,至第150min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150min(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。
Objective To investigate the effects of liraglutide, an analog of glucagon-like peptide-1 (GLP-1), on the expression of insulin receptor substrate-1 (IRS-1), nitric oxide and nitric oxide in human umbilical vein endothelial cells (HUVECs) (ENOS) and phosphorylated eNOS (p-eNOS) expression. Methods HUVECs were cultured in vitro with DMEM medium containing 5.5 mmol / L glucose. The cells were divided into 10 groups. Each group was treated with 3 nmol / L liraglutide injection at 0, 10, 15, The cells were extracted at 30, 45, 60, 90, 120, 150 and 180 minutes. The expressions of IRS-1, eNOS and p-eNOS in each group were detected by Western blot. Results Liraglutide had different expression of IRS-1 and p-eNOS in HUVECs at different time points. There was no significant difference in p-eNOS expression between 0, 10 and 15min (P> 0.05). The expression of p-eNOS gradually increased from the 30th minute to the 150th minute, and the expression of p-eNOS began to decline (P <0.05). The expression of IRS-1 was similar to that of p-eNOS, (P <0.05). However, there was no significant difference in the expression of eNOS between different time points (P> 0.05). Conclusion The GLP-1 analogue liraglutide can promote the expression of IRS-1 and p-eNOS in positive glucose-cultured HUVECs in a time-dependent manner. The effect peak of GLP-1 is 150 min, but not the eNOS expression.