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利拉鲁肽对缺氧和高糖状态下人脐静脉内皮细胞释放NO的影响及机制研究 被引量:2

Effect and Underlying Mechanism of Liraglutide on Nitrogen Monoxide Release in Human Umbilical Vein Endothelial Cells in the State of Hypoxia and High Glucose
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摘要 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(e NOS)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e NOS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e NOS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 ceils 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.
出处 《中国药师》 CAS 2017年第4期652-655,共4页 China Pharmacist
基金 湖北省知识创新专项(自然科学基金项目)(编号:2016CFB198) 湖北省卫计委科研项目(编号:WJ2017Q31)
关键词 胰高血糖素样肽-1 利拉鲁肽 内皮细胞 一氧化氮 一氧化氮合酶 Glucagon like peptide-1 Liraglutide Endothelial cells NO eNOS
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