Institute of Cardiovascular Sciences, St. Boniface Hospital Research, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.
J Cell Mol Med. 2012 Oct;16(10):2394-400. doi: 10.1111/j.1582-4934.2012.01554.x.
Sarpogrelate (SP), a serotonin (5-HT2A) receptor antagonist, is used as an anti-platelet agent for the treatment of some vascular diseases. SP has been reported to inhibit 5-HT induced coronary artery spasm, increase in intracellular calcium and smooth muscle cells proliferation. This study was undertaken to test that SP suppresses the development of atherosclerosis due to high cholesterol diet (HCD) by decreasing blood viscosity and oxidative stress. For this purpose, 29 rabbits were divided into four groups: control group (normal diet); normal diet group with SP at the dose of 5 mg/kg/day; HCD group fed 1% cholesterol; and HCD group with SP at the dose of 5 mg/kg/day. After 90 days of the experiment, blood samples were collected and the animals were killed; the thoracic aorta was stained by the Oil Red O staining method. The results indicate that plasma levels of cholesterol, triglycerides and malondialdehyde were increased in rabbits fed HCD. Plasma viscosity and whole blood viscosity were also higher in the HCD group than that in normal diet group. Treatment with SP prevented these alterations induced by HCD whereas this agent had no significant effect in rabbits fed normal diet. Morphological examination of the aorta revealed that SP treatment prevented the formation of foam cells and atherosclerotic plaque. It is suggested that the beneficial effects of SP in atherosclerosis may be due to actions on blood viscosity, lipid levels and oxidative stress.
沙格雷酯(SP)是一种 5-羟色胺(5-HT2A)受体拮抗剂,被用作抗血小板药物治疗一些血管疾病。已有报道称,SP 可抑制 5-HT 诱导的冠状动脉痉挛、细胞内钙增加和平滑肌细胞增殖。本研究旨在通过降低血液粘度和氧化应激来检验 SP 是否能抑制高胆固醇饮食(HCD)引起的动脉粥样硬化的发展。为此,将 29 只兔子分为四组:对照组(正常饮食);正常饮食组给予 SP 5mg/kg/天;HCD 组给予 1%胆固醇;HCD 组给予 SP 5mg/kg/天。实验 90 天后,采集血样并处死动物;用油红 O 染色法对胸主动脉进行染色。结果表明,HCD 喂养的兔子血浆胆固醇、甘油三酯和丙二醛水平升高。HCD 组的血浆粘度和全血粘度也高于正常饮食组。SP 治疗可预防 HCD 引起的这些改变,而在正常饮食组中,该药物无显著作用。主动脉形态学检查显示,SP 治疗可预防泡沫细胞和粥样斑块的形成。因此,SP 在动脉粥样硬化中的有益作用可能是由于对血液粘度、血脂水平和氧化应激的作用。