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目的:观察利拉鲁肽对缺氧和高糖状态下人脐静脉内皮细胞释放一氧化氮NO)的影响,并探讨其可能机制.方法:采用体外分离和培养的人脐静脉内皮细胞(HUVECs)建立缺氧和高糖模型,分别以利拉鲁肽、利拉鲁肽+exendin(9-39)孵育 HUVECs,通过MTT法测定各实验组细胞增殖活力、比色法测定乳酸脱氢酶(LDH)漏出量、硝酸还原酶法检测NO含量,以半定量RT-PCR技术检测各组细胞内皮型一氧化氮合酶(eNOS)基因表达情况.结果:利拉鲁肽能促进缺氧和高糖状态下HUVECs细胞增殖活力,减少LDH的漏出量,促进NO的释放和eNOS基因的表达(P<0.05或P<0.01).胰高血糖素样肽-1(GLP-1)受体阻断药exendin(9-39)可以部分抑制利拉鲁肽的上述作用(P<0.05).结论:利拉鲁肽能够改善缺氧和高糖状态下人脐静脉内皮细胞的内皮功能,其机制可能与上调eNOS基因表达、促进NO分泌有关.“,”Objective:To explore the effects and mechanism of liraglutide on nitrogen monoxide (NO) release in human umbilical vein endothelial cells in the state of hypoxia and high glucose.Methods:A model of hypoxia and high glucose was established by using isolation and culture of primary human umbilical vein endothelial cells (HUVECs) in vitro.HUVECs were incubated with liraglutide and/or exendin (9-39) for 4 h.The metabolic ability of cells was detected by MTT assay,the activity of lactate dehydrogenase (LDH) was measured by a colorimetric method,and the levels of extracellular NO were measured by a nitrate reductive enzymatic method.The endothelial nitric oxide synthase (eNOS) mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR).Results:Compared with the model group,liraglutide could significantly increase cell metabolic ability,reduce LDH release,increase NO release and eNOS mRNA expression (P<0.05 or P<0.01).The above effects of liraglutide were partly inhibited by glucagon like peptide-1 (GLP-1) receptor antagonist exendin (9-39)(P<0.05).Conclusion:Liraglutide can improve endothelial relaxation function in HUVECs in the state of hypoxia and high glucose in vitro.The effect might be related to up-regulating eNOS mRNA expression and promoting NO release.