Ezetimibe Attenuates Atherosclerosis Associated with Lipid Reduction and Inflammation Inhibition.
Ezetimibe Attenuates Atherosclerosis Associated with Lipid Reduction and Inflammation Inhibition.
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依折麦布可减轻与降脂和抑制炎症相关的动脉粥样硬化
DOI：
10.1371/journal.pone.0142430
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang JA
中科院分区：
文献类型：
--
作者：
Tie C;Gao K;Zhang N;Zhang S;Shen J;Xie X;Wang JA
Ezetimibe作为一种胆固醇吸收抑制剂，已被证明与他汀类药物联合使用可预防动脉粥样硬化。然而，还没有单独比较依折麦比和他汀类药物的有益效果。本研究旨在测试依折麦布单独使用是否会表现出与他汀类药物相似的效果，以及在中度病变大小的情况下是否需要联合治疗。方法与结果饲喂饱和脂肪补充饲料的ApoE-/-雄性小鼠，随机分为载药组、依泽替米贝单用组（10 mg/kg/d）、阿托伐他汀组（20 mg/kg/d）或依泽替米贝与阿托伐他汀联合饮水组。第28天处死小鼠，收集主动脉和血清，分析动脉粥样硬化病变和血脂、胆固醇水平。因此，ezetimibe单独对动脉粥样硬化病变大小的保护作用与阿托伐他汀相似，其机制是降低血清胆固醇浓度，抑制巨噬细胞在病变中的积聚，减少循环炎症细胞因子，如单核细胞趋化蛋白（MCP-1）和肿瘤坏死因子（TNF-α）。与依折替米贝给药相比，阿托伐他汀单独减轻动脉粥样硬化病变依赖于其抗炎作用。联合治疗和单药治疗（依折替米贝或阿托伐他汀）在病变面积和血清胆固醇、氧化LDL和炎症细胞因子浓度方面无显著差异。病变面积与血清胆固醇、MCP-1、TNF-α浓度呈显著相关。而TGF-β1和oxLDL的血清浓度与病变面积无显著相关性。结论Ezetimibe单用对中度动脉粥样硬化病变的保护作用与阿托伐他汀相同，可降低血清胆固醇，降低循环炎症因子，抑制巨噬细胞在病变中的积聚。
Background Ezetimibe, as a cholesterol absorption inhibitor, has been shown protecting against atherosclerosis when combined with statin. However, side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin. Herein, the study aimed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size. Methods and Results ApoE-/- male mice that were fed a saturated-fat supplemented diet were randomly assigned to different therapeutic regimens: vehicle, ezetimibe alone (10 mg/kg/day), atorvastatin (20 mg/kg/day) or combination of ezetimibe and atorvastatin through the drinking water. On 28 days, mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels. As a result, ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin, which was mediated by lowering serum cholesterol concentrations, inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines, such as monocyte chemoattractant protein (MCP-1) and tumor necrosis factor (TNF-α). In contrast to ezetimibe administration, atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects. There were no significance differences in lesion areas and serum concentrations of cholesterol, oxidized LDL and inflammatory cytokines between combination therapy and monotherapy (either ezetimibe or atorvastatin). There were significant correlations between the lesion areas and serum concentrations of cholesterol, MCP-1 and TNF-α, respectively. However, there were no significant correlations between the lesion areas and serum concentrations of TGF-β1 and oxLDL. Conclusions Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin, which was associated with lowering serum cholesterol, decreasing circulating inflammatory cytokines, and inhibiting macrophage accumulation in the lesions.