Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits.
Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits.
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DOI：
10.1186/1476-511x-12-166
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发表时间：
2013-11-04
影响因子：
4.5
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Niimi M;Keyamura Y;Nozako M;Koyama T;Kohashi M;Yasufuku R;Yoshikawa T;Fan J
普罗布考和他汀类药物通常用于治疗动脉粥样硬化。这两种药物表现出不同的机制，但尚不清楚它们是否具有相同的抗动脉粥样硬化特性。在当前的研究中，我们检查了这两种药物在最佳剂量下是否可以以相同的方式抑制胆固醇喂养的兔子动脉粥样硬化的发生。新西兰白兔被喂食富含胆固醇的食物 5 周，以产生动脉粥样硬化的早期病变。药物治疗的兔子服用普罗布考或阿托伐他汀，并将血清脂质和主动脉粥样硬化病变与对照组进行比较。与对照组相比，阿托伐他汀治疗显着降低了血清总胆固醇水平，而普罗布考治疗导致高密度脂蛋白胆固醇水平显着降低，而总胆固醇水平没有变化。与对照组相比，普罗布考治疗导致主动脉病变面积减少65%（p<0.01），而阿托伐他汀治疗导致主动脉病变面积减少23%（p=0.426）。组织学和免疫组织化学分析显示，与阿托伐他汀组和对照组相比，普罗布考治疗组的病变特点是单核细胞与内皮细胞的粘附明显减少，内膜巨噬细胞聚集明显减少。此外，从普罗布考组分离的低密度脂蛋白（LDL）表现出显着的抗氧化反应，而从阿托伐他汀治疗组或对照组分离的LDL中不存在这种反应。这项研究表明，普罗布考通过减少单核细胞粘附和浸润内膜下来抑制动脉粥样硬化的发生。普罗布考对 LDL 的抗氧化作用比他汀类药物介导的降脂作用更有效地防止早期病变形成。
Probucol and statin are often prescribed for treating atherosclerosis. These two drugs exhibit different mechanisms but it is unknown whether they have the same anti-atherogenic properties. In the current study, we examined whether these two drugs at optimal doses could inhibit the initiation of atherosclerosis in cholesterol-fed rabbits in the same way. New Zealand White rabbits were fed a cholesterol-rich diet for 5 weeks to produce the early-stage lesions of atherosclerosis. Drug-treated rabbits were administered either probucol or atorvastatin and serum lipids and aortic atherosclerotic lesions were compared with those in a control group. Atorvastatin treatment significantly reduced serum total cholesterol levels while probucol treatment led to significant reduction of high-density lipoprotein cholesterol levels without changing total cholesterol levels compared with those in the control group. Compared with the control, probucol treatment led to 65% (p < 0.01) reduction while atorvastatin treatment led to 23% (p = 0.426) reduction of the aortic lesion area. Histological and immunohistochemical analyses revealed that the lesions of the probucol-treated group were characterized by remarkable reduction of monocyte adherence to endothelial cells and macrophage accumulation in the intima compared with those of both atorvastatin and control groups. Furthermore, low-density lipoprotein (LDL) isolated from the probucol group exhibited prominent anti-oxidative reaction, which was not present in LDL isolated from either the atorvastatin-treated or the control group. This study suggests that probucol inhibits the initiation of atherosclerosis by reducing monocyte adherence and infiltration into the subintima. Anti-oxidization of LDL by probucol protects more effectively against early-stage lesion formation than statin-mediated lipid-lowering effects.