A role for diallyl trisulfide in mitochondrial antioxidative stress contributes to its protective effects against vascular endothelial impairment
A role for diallyl trisulfide in mitochondrial antioxidative stress contributes to its protective effects against vascular endothelial impairment
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二烯丙基三硫化物在线粒体抗氧化应激中的作用有助于其对血管内皮损伤的保护作用
DOI：
10.1016/j.ejphar.2014.01.010
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发表时间：
2014-02-15
影响因子：
5
通讯作者：
Huang, Qi-Ren
中科院分区：
文献类型：
--
作者：
Liu, Li-Li;Yan, Li;Huang, Qi-Ren
持续的高血糖会增加全身氧化应激，导致血管内皮功能障碍和动脉粥样硬化的发生。二烯丙基三硫(DAT)是大蒜中的一种天然有机硫化合物，具有扩张血管和抗菌等作用。本研究采用体内肥胖糖尿病大鼠模型和高糖诱导的血管内皮细胞损伤模型，研究DAT对血管内皮细胞损伤的保护作用及其机制。在体内模型中，肥胖糖尿病大鼠分别静脉注射DAT(5.0 mg kg~(-1)d~(-1))和维生素E(1.0 mg kg~(-1)d~(-1))，每日1次，连续7d。在体外培养的HG损伤的人脐静脉内皮细胞中，分别加入或不加入DAT(25mU/L L-1，50mU/L L-1100mU/L L)或维生素E(25mU/L L-1)作用24 h，观察血管内皮损伤的程度及DAT的保护作用。体内和体外实验结果表明，DAT处理可明显减轻血管内皮细胞损伤。此外，DAT处理显著降低了线粒体中丙二醛(NADA)和活性氧的水平，而提高了超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性。此外，DAT处理显著改善了线粒体的呼吸功能。综上所述，我们的结果表明，DAT通过减少线粒体氧化应激来保护血管内皮细胞免受HG或高血糖所致的损伤。这一发现为DAT潜在地治疗氧化应激疾病，即动脉粥样硬化、糖尿病和神经退行性疾病提供了新的见解。(C)2014 Elsevier B.V.保留所有权利，
Persistent hyperglycemia increases a systemic oxidative stress, causing the onset of vascular endothelial dysfunction and atherosclerosis. Diallyl trisulfide (DAT), a natural organosulfur compound in garlic, has been reported to have actions of dilating blood vessels and antibacteria, etc. In this study, models of obese diabetic rat in vivo and high glucose concentration (HG)-induced endothelial cell injury in vitro were used to investigate the protective effects of DAT on vascular endothelial injury and its underlying mechanisms. In the in vivo model, the obese diabetic rats were injected venously with DAT (5.0 mg kg(-1) d(-1)) and Vitamin E (1.0 mg kg(-1) d(-1)) respectively, once daily for 7 consecutive days. In the in vitro model, HG-injured HUVEC were treated with or without DAT (25 mu mol L-1, 50 mu mol L-1 100 mu mol L-1) or Vitamin E (25 mu mol L-1) respectively for 24 h. The extents of vascular endothelial injury and protective effects of DAT were evaluated. The results both in vivo and in vitro displayed that DAT-treatment significantly attenuated the endothelial cell impairments. Besides, DAT-treatment markedly decreased the levels of malondialdehyde (NADA) and reactive oxygen species, whereas elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondrium. Moreover, DAT-treatment considerably improved mitochondrial respiration function. Taken together, our results suggest that DAT protects vascular endothelium from HG or hyperglycemia induced-injury by reducing mitochonclrial oxidative stress. The findings provide a novel insight for DAT to potentially treat the oxidative stress diseases, i.e., atherosclerosis, diabetes, and neuroclegenerative diseases. (C) 2014 Elsevier B.V. All rights reserved,