西格列汀对人主动脉内皮细胞内皮素1及一氧化氮合酶的影响及其机制
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作者单位:

(安徽医科大学第一附属医院心内科,安徽省合肥市 230032)

作者简介:

戴尧,博士,医师,研究方向为动脉粥样硬化,E-mail为daiyaoh@163.com。林先和,博士,主任医师,研究方向为动脉粥样硬化。戴东生,博士,主任医师,研究方向为动脉粥样硬化。

基金项目:

国家自然科学基金青年科学基金培养计划项目(2013KJ25);安徽省自然科学基金面上项目(1508085MH178)


Sitagliptin Regulates Endothelin-1 and Nitric Oxide Synthase Through Inhibiting Phosphorylation of NF-κB in Human Aortic Endothelial Cells
Author:
Affiliation:

Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, China)

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    摘要:

    目的 探讨在高糖培养环境下西格列汀对人主动脉内皮细胞(HAEC)内皮素1及一氧化氮合酶的影响及其可能机制。方法 高糖环境下(25 mmol/L葡萄糖)培养人主动脉内皮细胞,并分别给予0、5、10及20 μmol/L西格列汀干预,检测HAEC内皮型一氧化氮合酶(eNOS)、内皮素1(ET-1)、诱导型一氧化氮合酶(iNOS)以及核因子κB p65(NF-κB p65)的mRNA和蛋白表达水平;应用肿瘤坏死因子α(TNF-α)处理西格列汀干预后的HAEC,观察eNOS、ET-1、iNOS、NF-κB p65的mRNA和蛋白表达水平的变化。结果 与普通培养环境(7 mmol/L葡萄糖)相比,高糖环境下HAEC的eNOS mRNA和蛋白表达降低,ET-1、iNOS mRNA和蛋白表达及p-NF-κB p65蛋白表达增高(P<0.05)。与0 μmol/L组相比,20 μmol/L西格列汀组HAEC的eNOS mRNA、蛋白表达上调,ET-1、iNOS mRNA和蛋白表达以及p-NF-κB p65蛋白表达下调(P<0.05)。与单独使用西格列汀组相比,TNF-α联合西格列汀组HAEC的eNOS mRNA和蛋白表达下调,ET-1、iNOS mRNA和蛋白表达及p-NF-κB p65蛋白表达上调(P<0.05)。结论 西格列汀在转录和翻译水平上增加eNOS表达、降低ET-1、iNOS的表达,该作用通过其抑制p-NF-κB p65表达而实现。提示西格列汀可能改善内皮功能,从而预防糖尿病动脉粥样硬化的形成。

    Abstract:

    Aim To explore the effect of sitagliptin on the expression of endothelin-1(ET-1) and endothelial nitric oxide synthase(eNOS) in human aortic endothelial cells(HAEC) and its underlying mechanism in high glucose environment. Methods HAEC were cultured in high glucose environment(25 mmol/L), and treated with different concentrations of sitagliptin(0, 5, 10 and 20 μmol/L, respectively). The mRNA and protein expressions of eNOS, ET-1, iNOS and phosphate nuclear factor-kappa B p65(p-NF-κB p65) were measured. The measurements for eNOS, ET-1, iNOS, NF-κB p65 on mRNA and protein levels in HAEC were evaluated after incubation with tumor necrosis factor-α(TNF-α) and sitagliptin. Results Compared with normal medium(glucose concentrations for 7 mmol/L), both the mRNA and the protein expression of eNOS in HAEC significantly decreased in high glucose medium, while those of ET-1, iNOS and p-NF-κB p65 protein significantly increased(P<0.05). Compared with 0 μmol/L sitagliptin, 20 μmol/L sitagliptin significantly increased mRNA and protein expressions of eNOS, while decreased those of ET-1, iNOS and p-NF-κB p65 protein(P<0.05). Compared with sitagliptin alone treated HAEC, both the mRNA and the protein expressions of eNOS significantly decreased in HAEC treated with TNF-α and sitagliptin, while those of ET-1, iNOS and p-NF-κB p65 protein expressions significantly increased(P<0.05). Conclusions Sitagliptin enhances eNOS, represses ET-1, iNOS expressions at the level of transcription and translation through inhibiting NF-κB p65 phosphorylation in HAEC in high glucose environment. This may contribute to the improvement of endothelial function and prevention of subsequent atherogenesis.

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引用本文

戴尧,林先和,戴东生.西格列汀对人主动脉内皮细胞内皮素1及一氧化氮合酶的影响及其机制[J].中国动脉硬化杂志,2016,24(2):114~118.

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  • 收稿日期:2015-04-13
  • 最后修改日期:2015-07-14
  • 在线发布日期: 2016-06-30