The Endothelial Protective Properties of Essential Oil from Fructus Alpiniae zerumbet via the Akt/NOS-NO Signaling Pathway In Vitro
The Endothelial Protective Properties of Essential Oil from Fructus Alpiniae zerumbet via the Akt/NOS-NO Signaling Pathway In Vitro
复制标题
高山姜精油通过 Akt/NOS-NO 信号通路的体外内皮保护特性
DOI：
10.1055/s-0034-1383129
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发表时间：
2014-11-01
期刊：
影响因子：
2.7
通讯作者：
Shen, Xiangchun
中科院分区：
文献类型：
--
作者：
Xiao, Tingting;Zeng, Yu;Shen, Xiangchun
氧化低密度脂蛋白至少部分通过一氧化氮依赖性途径诱导血管损伤。我们前期的研究表明，高山姜挥发油具有抗氧化作用，能改善离体血管内皮功能和舒张血管。本研究的目的是证实这一假设，高良姜对氧化低密度脂蛋白诱导的人主动脉内皮细胞的内皮功能障碍的保护，和一氧化氮合酶在这个过程中发挥的作用。人主动脉内皮细胞用三种不同剂量的益智仁（1、2或4 µg/mL）、辛伐他汀（10 µM）或溶剂预处理，然后与氧化低密度脂蛋白（150 µg/mL）共孵育设计的时间段。暴露于氧化低密度脂蛋白导致细胞毒性伴随着线粒体膜电位崩溃，过量的活性氧的产生，和减少一氧化氮的生产。诱导型一氧化氮合酶mRNA和蛋白表达的上调分别通过逆转录-聚合酶链反应和Western印迹分析确定。氧化低密度脂蛋白抑制Akt磷酸化，下调内皮型一氧化氮合酶和可溶性鸟苷酸环化酶的mRNA表达和蛋白水平。而益智仁或Sim预处理可显著抑制氧化型低密度脂蛋白引起的细胞毒性及活性氧和一氧化氮的异常生成。本研究结果证实了益智仁通过抗氧化和调节Akt/一氧化氮合酶-一氧化氮信号通路对氧化低密度脂蛋白诱导的内皮功能障碍具有保护作用。
Abstract Oxidized low-density lipoprotein has been demonstrated to induce vascular injury, at least partly, through the nitric oxide-dependent pathway. Our previous studies showed that the essential oil from Fructus Alpiniae zerumbet had a capacity of antioxidation to ameliorate endothelial function and vasodilatation on aortic rings ex vivo. The present study aims to confirm the hypothesis that Fructus Alpiniae zerumbet protects against oxidized low-density lipoprotein-induced endothelial dysfunction in human aortic endothelial cells, and the role nitric oxide synthase plays in the process. Human aortic endothelial cells were pretreated with one of three different doses of Fructus Alpiniae zerumbet (1, 2, or 4 µg/mL), simvastatin (10 µM), or vehicle,followed by coincubation with oxidized low-density lipoprotein (150 µg/mL), for designed time periods. Exposure to oxidized low-density lipoprotein resulted in cytotoxicity accompanied by mitochondrial membrane potential collapse, excessive reactive oxygen species generation, and a decrease of nitric oxide production. The upregulation of inducible nitric oxide synthase mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. Furthermore, oxidized low-density lipoprotein inhibited Akt phosphorylation and downregulated endothelial nitric oxide synthase and soluble guanylatecyclase in mRNA expression and the protein level. However, cytotoxicity and aberrant reactive oxygen species and nitric oxide generation caused by oxidized low-density lipoprotein could be significantly inhibited by Fructus Alpiniae zerumbet or Sim pretreatment. Results from this study confirmed that Fructus Alpiniae zerumbet could protect against oxidized low-density lipoprotein-induced endothelial dysfunction by antioxidation and modulating the Akt/nitric oxide synthase-nitric oxide signaling pathway.