Quercetin improves macrophage reverse cholesterol transport in apolipoprotein E-deficient mice fed a high-fat diet.
Quercetin improves macrophage reverse cholesterol transport in apolipoprotein E-deficient mice fed a high-fat diet.
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DOI：
10.1186/s12944-016-0393-2
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发表时间：
2017-01-14
影响因子：
4.5
通讯作者：
Guo S
中科院分区：
文献类型：
--
作者：
Cui Y;Hou P;Li F;Liu Q;Qin S;Zhou G;Xu X;Si Y;Guo S
槲皮素是植物中分布最广泛的类黄酮之一，已被证明可以减少动脉粥样硬化和动脉粥样硬化病变的形成。胆固醇逆向转运（RCT）在外周血细胞胆固醇输出中起着至关重要的作用，这是预防和治疗动脉粥样硬化的一种机制。本研究的目的是研究槲皮素是否通过改善RCT来减少体内脂质蓄积。以高脂饮食喂养的载脂蛋白E缺陷小鼠为研究对象，采用同位素示踪法研究槲皮素对RCT的影响，并通过分子生物学技术阐明其作用机制。这些新的结果表明，槲皮素显著改善了[3 H]-胆固醇从[3 H]-胆固醇负载的巨噬细胞转移到血浆（增加约34%），肝脏（增加30%）和胆汁（增加50%），最终转移到粪便（增加约40%），用于高脂饮食喂养的载脂蛋白E缺陷小鼠的排泄。槲皮素还能显著提高血浆和高密度脂蛋白（HDL）对胆固醇的接受能力，显著降低血浆中丙二醛含量和HDL携带的氧化磷酸胆碱。因此，槲皮素改善RCT的潜在机制可能部分是由于HDL的胆固醇接受能力提高，RCT相关蛋白如ATP结合盒（ABC）A1和G1的表达水平增加，以及HDL的抗氧化活性提高。槲皮素在动脉粥样硬化模型中加速RCT，这有助于阐明槲皮素的降脂作用。
Quercetin, one of the most widely distributed flavonoids in plants, has been demonstrated to reduce hyperlipidaemia and atherosclerotic lesion formation. Reverse cholesterol transport (RCT) plays a crucial role in exporting cholesterol from peripheral cells, which is one mechanism utilized in the prevention and treatment of atherosclerosis. The aim of this study is to investigate whether quercetin reduces lipid accumulation by improving RCT in vivo. Apolipoprotein E-deficient mice fed a high-fat diet were used to investigate the effect of quercetin on RCT by an isotope tracing method, and the underlying mechanisms were clarified by molecular techniques. These novel results demonstrated that quercetin significantly improved [3H]-cholesterol transfer from [3H]-cholesterol-loaded macrophages to the plasma (approximately 34% increase), liver (30% increase), and bile (50% increase) and finally to the feces (approximately 40% increase) for excretion in apolipoprotein E-deficient mice fed a high-fat diet. Furthermore, quercetin markedly increased the cholesterol accepting ability of plasma and high-density lipoprotein (HDL) and dramatically decreased the content of malondialdehyde in plasma and oxidized phosphocholine carried by HDL. Therefore, the underlying mechanisms of quercetin in improving RCT may be partially due to the elevated cholesterol accepting ability of HDL, the increased expression levels of proteins related to RCT, such as ATP-binding cassettes (ABC) A1 and G1, and the improved antioxidant activity of HDL. Quercetin accelerates RCT in an atherosclerosis model, which is helpful in clarifying the lipid-lowering effect of quercetin.