The inhibitory effect of soy protein isolate on atherosclerosis in mice does not require the presence of LDL receptors or alteration of plasma lipoproteins
The inhibitory effect of soy protein isolate on atherosclerosis in mice does not require the presence of LDL receptors or alteration of plasma lipoproteins
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DOI：
10.1093/jn/132.1.43
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发表时间：
2002-01-01
影响因子：
4.2
通讯作者：
Williams, JK
中科院分区：
文献类型：
--
作者：
Adams, MR;Golden, DL;Williams, JK
饮食大豆有利于影响脂蛋白代谢和抑制动脉粥样硬化的机制尚不确定。对血液单个核细胞和培养的肝细胞的研究表明，某些大豆多肽(即7S球蛋白)可以刺激低密度脂蛋白受体的表达。这一途径代表了一种假想的机制，大豆的降胆固醇和抗动脉粥样硬化作用可能是通过这种机制来实现的。然而，缺乏支持这一假设的直接证据。为了解决这个问题，我们比较了饮食中大豆分离蛋白在两种基因工程小鼠动脉粥样硬化模型中的效果。其中一只小鼠[低密度脂蛋白受体-/-载脂蛋白B转基因]缺乏低密度脂蛋白受体并过度产生载脂蛋白B，而另一只小鼠(载脂蛋白E-/-)具有正常的低密度脂蛋白受体但不产生载脂蛋白E。有三个处理组，主要根据饲料蛋白质成分的来源而不同：1)酪蛋白/乳清蛋白(不含异黄酮)，2)醇洗大豆分离蛋白(总异黄酮量=0.04 mg/g)，3)完整大豆分离蛋白(总异黄酮量=1.72 mg/g)。动脉粥样硬化的评估是通过量化主动脉中酯化胆固醇的含量来进行的。乙醇洗涤(45%和31%)(P<；0.05)和完整大豆分离蛋白(65%和41%)(P<；0.05)可抑制低密度脂蛋白受体-/-和载脂蛋白E-/-小鼠的动脉粥样硬化(相对于酪蛋白/乳白蛋白组)。没有性别差异。在双向分析中，大豆分离物的类型和老鼠的类型有显著的影响。低密度脂蛋白受体/-小鼠(P<；0.001)的抗动脉粥样硬化作用增强，而饲喂酒精洗涤大豆分离蛋白的小鼠(P<；0.001)的抗动脉粥样硬化作用减弱。此外，大豆对动脉粥样硬化的抑制作用与血浆低密度脂蛋白、极低密度脂蛋白或高密度脂蛋白的浓度无关。这些结果直接证明了存在依赖低密度脂蛋白受体和血浆脂蛋白的途径，饮食中的大豆分离蛋白通过这些途径抑制动脉粥样硬化。
The mechanisms by which dietary soy favorably influences lipoprotein metabolism and inhibits atherosclerosis are uncertain. Studies of blood mononuclear cells and cultured hepatocytes have indicated that certain soy peptides; (i.e., 7S globulins) stimulate expression of LDL receptors. This pathway represents a hypothetical mechanism by which soy's hypocholesterolemic and antiatherosclerotic effects may be mediated. However, direct evidence supporting this hypothesis is lacking. To address this, we compared effects of dietary soy protein isolate in two genetically engineered mouse models of atherosclerosis. One mouse [LDL receptor -/- apolipoprotein (apo) B transgenic] is devoid of LDL receptors and overproduces apolipoprotein B, whereas the other (apoE -/-) has a normal complement of LDL receptors but does not produce apolipoprotein E. Male (n = 10-12/group) and ovariectomized female (n = 10-12/group) mice were studied. There were three treatment groups, which differed principally by the source of the protein component of the diet: 1) casein/lactalbumin (no isoflavones), 2) alcohol-washed soy protein isolate (total isoflavones = 0.04 mg/g), and 3) intact soy protein isolate (total isoflavones = 1.72 mg/g). Atherosclerosis was assessed by quantifying the aortic content of esterified cholesterol. Atherosclerosis was inhibited (relative to the casein/lactalbumin group) by both alcohol-washed (45 and 31 %) (P < 0.05) and intact (65 and 41 %) (P < 0.05) soy protein isolate in LDL receptor -/- and apoE -/- mice, respectively. There was no sex difference. In a two-way analysis, there were significant effects of type of soy isolate and type of mouse. The antiatherosclerosis effect was enhanced in LDL receptor -/- mice (P < 0.001) and diminished in mice fed alcohol-washed soy protein isolate (P < 0.001). Furthermore, inhibitory effects of soy on atherosclerosis were unrelated to plasma LDL, VLDL or HDL cholesterol concentrations. The results represent direct evidence for the existence of LDL receptor- and plasma lipoprotein-independent pathways by which dietary soy protein isolate inhibits atherosclerosis.