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血竭,一种龙血树脂,可减轻高糖诱导的人脐静脉内皮细胞氧化应激和内皮功能障碍。

Sanguis draconis, a dragon's blood resin, attenuates high glucose-induced oxidative stress and endothelial dysfunction in human umbilical vein endothelial cells.

作者信息

Chang Yi, Chang Ting-Chen, Lee Jie-Jen, Chang Nen-Chung, Huang Yung-Kai, Choy Cheuk-Sing, Jayakumar Thanasekaran

机构信息

Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Road, Taipei 101, Taiwan ; School of Medicine, Fu-Jen Catholic University, 510 Zhong-Zheng Road, Taipei 205, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Department of Lymphatic Vascular Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan.

出版信息

ScientificWorldJournal. 2014;2014:423259. doi: 10.1155/2014/423259. Epub 2014 Jun 2.

Abstract

Hyperglycaemia, a characteristic feature of diabetes mellitus, induces endothelial dysfunction and vascular complications by limiting the proliferative potential of these cells. Here we aimed to investigate the effect of an ethanolic extract of Sanguis draconis (SD), a kind of dragon's blood resin that is obtained from Daemonorops draco (Palmae), on human umbilical vein endothelial cells (HUVEC) under high-glucose (HG) stimulation and its underlying mechanism. Concentration-dependent (0-50 μg/mL) assessment of cell viability showed that SD does not affect cell viability with a similar trend up to 48 h. Remarkably, SD (10-50 μg/mL) significantly attenuated the high-glucose (25 and 50 mM) induced cell toxicity in a concentration-dependent manner. SD inhibited high glucose-induced nitrite (NO) and lipid peroxidation (MDA) production and reactive oxygen species (ROS) formation in HUVEC. Western blot analysis revealed that SD treatments abolished HG-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2), nuclear transcription factor, κB (NF-κB), VCAM-1, and E-selectin, and it also blocked the breakdown of PARP-116 kDa protein in a dose-dependent manner. Furthermore, we found that SD increased the expression of Bcl-2 and decreased Bax protein expression in HG-stimulated HUVEC. Thus, these results of this study demonstrate for the first time that SD inhibits glucose induced oxidative stress and vascular inflammation in HUVEC by inhibiting the ERK/NF-κB/PARP-1/Bax signaling cascade followed by suppressing the activation of VCAM-1 and E-selectin. These data suggest that SD may have a therapeutic potential in vascular inflammation due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activation.

摘要

高血糖是糖尿病的一个特征性表现,它通过限制这些细胞的增殖潜能来诱导内皮功能障碍和血管并发症。在此,我们旨在研究血竭(SD)的乙醇提取物(血竭是一种从麒麟竭(棕榈科)中提取的龙血树脂)在高糖(HG)刺激下对人脐静脉内皮细胞(HUVEC)的影响及其潜在机制。细胞活力的浓度依赖性(0 - 50μg/mL)评估表明,在长达48小时内,SD对细胞活力没有影响,呈现相似趋势。值得注意的是,SD(10 - 50μg/mL)以浓度依赖性方式显著减轻了高糖(25和50mM)诱导的细胞毒性。SD抑制了高糖诱导的HUVEC中亚硝酸盐(NO)和脂质过氧化(MDA)的产生以及活性氧(ROS)的形成。蛋白质印迹分析显示,SD处理消除了HG诱导的细胞外信号调节激酶1/2(ERK 1/2)、核转录因子κB(NF-κB)、血管细胞黏附分子-1(VCAM-1)和E-选择素的磷酸化,并且还以剂量依赖性方式阻断了聚(ADP-核糖)聚合酶-1 116kDa蛋白的降解。此外,我们发现SD增加了HG刺激的HUVEC中Bcl-2的表达并降低了Bax蛋白的表达。因此,本研究的这些结果首次证明,SD通过抑制ERK/NF-κB/PARP-1/Bax信号级联反应,随后抑制VCAM-1和E-选择素的激活,从而抑制了葡萄糖诱导的HUVEC氧化应激和血管炎症。这些数据表明,由于氧化应激、细胞凋亡和PARP-1激活水平的降低,SD可能在血管炎症方面具有治疗潜力。

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