First Institute of New Drug Discovery, Otsuka Pharmaceutical Co, Ltd, Tokushima, Japan.
PLoS One. 2012;7(6):e39374. doi: 10.1371/journal.pone.0039374. Epub 2012 Jun 22.
Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities.
西洛他唑临床上用于治疗慢性外周动脉阻塞患者的缺血症状和脑梗死的二级预防。最近有报道称，西洛他唑对动脉粥样硬化形成和降低啮齿动物模型中的血清甘油三酯具有预防作用。然而，关于使用动脉粥样硬化兔评估西洛他唑的报道很少，这些兔的脂代谢与人相似，用于研究高脂血症条件下主动脉中的脂质含量和血小板聚集。因此，我们评估了西洛他唑对正常饮食或添加胆固醇饮食的兔子的动脉粥样硬化和血小板聚集的影响，添加或不添加西洛他唑。我们通过测量血清和主动脉脂质含量以及 10 周治疗后的病变面积来评估西洛他唑对动脉粥样硬化形成的影响，并通过 1 周和 10 周治疗后的血小板聚集来评估其对血小板聚集的影响。从脂质分析来看，西洛他唑显著降低了血清中的总胆固醇、甘油三酯和磷脂，而且还降低了动脉粥样硬化主动脉中的甘油三酯含量。西洛他唑显著减少了内膜动脉粥样硬化面积。胆固醇喂养的兔子的血小板聚集增强。西洛他唑显著抑制了正常饮食和高胆固醇饮食喂养的兔子的血小板聚集。西洛他唑可能通过改善脂代谢和抑制血小板活化，对胆固醇喂养的兔子具有抗动脉粥样硬化和抗血小板作用。结果表明，西洛他唑对脂代谢异常的动脉粥样硬化血栓形成性疾病具有预防和治疗作用。
