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

发布时间：2018-04-02 22:24

本文选题：西格列汀　切入点：内皮型一氧化氮合酶　出处：《中国动脉硬化杂志》2016年02期

【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20μmol/L西格列汀干预,检测HAEC内皮型一氧化氮合酶(e NOS)、内皮素1(ET-1)、诱导型一氧化氮合酶(i NOS)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e NOS、ET-1、i NOS、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e NOS mRNA和蛋白表达降低,ET-1、i NOS mRNA和蛋白表达及p-NF-κB p65蛋白表达增高(P0.05)。与0μmol/L组相比,20μmol/L西格列汀组HAEC的e NOS mRNA、蛋白表达上调,ET-1、i NOS mRNA和蛋白表达以及p-NF-κB p65蛋白表达下调(P0.05)。与单独使用西格列汀组相比,TNF-α联合西格列汀组HAEC的e NOS mRNA和蛋白表达下调,ET-1、i NOS mRNA和蛋白表达及p-NF-κB p65蛋白表达上调(P0.05)。结论西格列汀在转录和翻译水平上增加e NOS表达、降低ET-1、i NOS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]:Objective to investigate the effect of siglitatin on endothelin 1 and nitric oxide synthase (NOS) in cultured human aortic endothelial cells (HAECs) and its possible mechanism.Methods Human aortic endothelial cells were cultured in high glucose (25 mmol/L glucose) and were treated with siglitazine at 10 渭 mol/L and 20 渭 mol/L, respectively.The expression levels of mRNA and protein in HAEC endothelial nitric oxide synthase (HAEC), endothelin 1 (et 1), inducible nitric oxide synthase (iNOS) and nuclear factor 魏 B p65 (NF- 魏 B p65) were detected.HAECs were treated with tumor necrosis factor- 伪 (TNF- 伪), and the expression of mRNA and protein in eNOSS-ET-1 / I NOSN NF- 魏 B p65 was observed.Results compared with normal culture environment (7 mmol/L glucose), the expression of e NOS mRNA and protein in HAEC was lower than that in normal culture environment. The expression of NOS mRNA and protein and the expression of p-NF- 魏 B p65 protein were significantly increased in HAEC.Compared with 0 渭 mol/L group, the e NOS mRNAs of HAEC in 20 渭 mol/L siglitatin group were up-regulated, the expression of NOS mRNA and protein were up-regulated, and the expression of p-NF- 魏 B p65 was down-regulated (p0.05).Conclusion siglitatin can increase the expression of e NOS and decrease the expression of ET-1 NOS at the level of transcription and translation, which can be achieved by inhibiting the expression of p-NF- 魏 B p65.It suggests that siglitatin may improve endothelial function and prevent the formation of diabetic atherosclerosis.
【作者单位】：安徽医科大学第一附属医院心内科;
【基金】：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)
【分类号】：R96

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