Probucol and cilostazol exert a combinatorial anti-atherogenic effect in cholesterol-fed rabbits
Probucol and cilostazol exert a combinatorial anti-atherogenic effect in cholesterol-fed rabbits
复制标题
普罗布考和西洛他唑对胆固醇喂养的兔子发挥联合抗动脉粥样硬化作用。
DOI：
10.1016/j.thromres.2013.09.007
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发表时间：
2013-11-01
影响因子：
7.5
通讯作者：
Liu, Enqi
中科院分区：
文献类型：
--
作者：
Chen, Yulong;Zhao, Sihai;Liu, Enqi
前言：普罗布考(PB)和西洛他唑(CZ)均具有抗动脉粥样硬化作用。然而，它们的组合效应尚不清楚。本研究旨在研究它们的联合抗动脉粥样硬化作用。材料和方法：给兔喂饲含PB或CZ或同时含PB和CZ的胆固醇饲料16周。测定血浆总胆固醇、低密度脂蛋白、高密度脂蛋白、C反应蛋白、超氧化物歧化酶、丙二醛和一氧化氮(NO)水平。大体和显微镜下评价动脉粥样硬化病变。结果与结论：与赋形剂组相比，PB组和PB+CZ组的病变面积缩小(PB+CZ组为70%，PB组为56%)。然而，虽然PB单独和PB+CZ导致了病变面积的缩小，但组织学分析显示，与赋形剂组相比，只有PB+CZ显著减少了病变中巨噬细胞的聚集和平滑肌细胞的增殖。PB+CZ组大鼠血浆总胆固醇水平明显低于空白对照组，且PB+CZ具有明显的抗氧化抗炎作用。有趣的是，PB+CZ处理导致血浆NO水平显著升高。体外实验表明，联合用药可上调氧化型低密度脂蛋白作用下内皮细胞的NO水平和蛋白S亚硝化水平。综上所述，这些结果表明PB和CZ具有联合抗动脉粥样硬化作用。(C)2013年提交人。爱思唯尔有限公司出版。保留所有权利。
Introduction: Probucol (PB) and cilostazol (CZ) both exhibit anti-atherogenic effects. However, their combinatorial effects are unclear. This study was designed to investigate their combinatorial anti-atherogenic effect in cholesterol-fed rabbits.Materials and Methods: Rabbits were fed a cholesterol diet with PB or CZ alone or both PB and CZ for 16 weeks. The plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, C-reactive protein, superoxide dismutase, malondialdehyde, and nitric oxide (NO) were measured. The aortic atherosclerotic lesions were grossly and microscopically evaluated. Additionally, in vitro experimentswere conducted using human umbilical vein endothelial cells.Results and Conclusion: We found that the PB group and the PB + CZ group exhibited a reduction in the lesion areas (70% in the PB + CZ group, 56% in the PB group) compared with the vehicle group. However, although PB alone and PB + CZ led to a reduction in the lesion size, the histological analysis revealed that only PB + CZ significantly decreased the macrophage accumulation and smooth muscle cell proliferation in the lesions compared with the vehicle group. The plasma levels of total cholesterol in the PB + CZ group were decreased compared with the vehicle group, Moreover, PB + CZ exerted obvious anti-oxidant and anti-inflammatory effects. Interestingly, the PB + CZ treatment led to amarked increase in the levels of plasmaNO. The in vitro experiments showed that the combinatorial treatment up-regulated the levels of NO and protein S-nitrosylation in endothelial cells treated with oxidized LDL. In summary, these results suggest that PB and CZ exert combinatorial antiatherogenic effects. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.