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Protective role of alpha-lipoic acid in hyperuricemia-induced endothelial dysfunction

机译:α-硫辛酸在高温血症诱导的内皮功能障碍中的保护作用

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摘要

The aim of the current study was to determine the effects of alpha-lipoic acid (LA) on hyperuricemia and endothelial dysfunction, and to uncover the underlying mechanism of its action. A hyperuricemic rat model was established by administration of uric acid (UA) and the rats were orally fed with 2 g/kg/day LA or phosphate-buffered saline. Primary rat aortic endothelial cells were subsequently isolated, and a cell viability assay, apoptosis assay, enzyme nitric oxide synthase (eNOS) activity assay and mitochondrial function assay were all performed. For the in vitro study, human umbilical vein endothelial cells were used and western blotting was performed to assess Akt signaling activity. The results of the current study indicated that LA inhibited apoptosis, enhanced eNOS activity and production of nitric oxide (NO), and rescued mitochondrial mass and function in uric acid (UA)-treated endothelial cells. LA activated Akt signaling and inhibition of Akt signaling abolished the effects of LA on cell viability, NO production, ROS production and ATP levels in UA-treated endothelial cells. Therefore, the current study demonstrated that LA attenuated oxidant stress and inhibited apoptosis in UA-treated endothelial cells by activating Akt signaling. The results indicate that LA may serve as a therapeutic approach to treat hyperuricemia-induced endothelial dysfunction.
机译:目前研究的目的是确定α-硫辛酸(LA)对高尿酸血症和内皮功能障碍的影响,并揭示其作用的潜在机制。通过尿酸(UA)建立了一种高发性大鼠模型,并用2g / kg /季La或磷酸盐缓冲盐水口服大鼠。随后分离初级大鼠主动脉内皮细胞,并进行细胞活力测定,细胞凋亡测定,酶一氧化氮合酶(Enos)活性测定和线粒体功能测定和线粒体功能测定。对于体外研究,使用人的脐静脉内皮细胞,进行Western印迹以评估AKT信号传导活性。目前研究的结果表明,LA抑制凋亡,增强的eNOS活性和一氧化氮(NO)的产生,并拯救了尿酸(UA) - 治疗内皮细胞的线粒体质量和功能。 LA激活的AKT信号传导和AKT信号传导的抑制废除了LA对UA处理的内皮细胞中的细胞活力,没有生产,ROS产生和ATP水平的影响。因此,目前的研究表明,通过激活AKT信号传导,La减弱氧化剂应力并抑制UA处理的内皮细胞中的凋亡。结果表明,LA可以作为治疗高温血症诱导的内皮功能障碍的治疗方法。

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  • 作者单位

    Heilongjiang Prov Hosp Dept Cardiol 82 Zhongshan St Harbin 150000 Heilongjiang Peoples R China;

    Heilongjiang Prov Hosp Dept Cardiol 82 Zhongshan St Harbin 150000 Heilongjiang Peoples R China;

    Heilongjiang Prov Hosp Dept Cardiol 82 Zhongshan St Harbin 150000 Heilongjiang Peoples R China;

    Heilongjiang Prov Hosp Dept Cardiol 82 Zhongshan St Harbin 150000 Heilongjiang Peoples R China;

    Heilongjiang Prov Hosp Dept Cardiol 82 Zhongshan St Harbin 150000 Heilongjiang Peoples R China;

    Heilongjiang Prov Hosp Dept Cardiol 82 Zhongshan St Harbin 150000 Heilongjiang Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 治疗学;
  • 关键词

    hyperuricemia; endothelial dysfunction; lipoic acid; apoptosis; Akt signaling;

    机译:hydercaricemia;内皮功能障碍;硫辛酸;细胞凋亡;AKT信号传导;

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