Adams Michael R, Golden Deborah L, Anthony Mary S, Register Thomas C, Williams J Koudy
Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
J Nutr. 2002 Jan;132(1):43-9. doi: 10.1093/jn/132.1.43.
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.
膳食大豆对脂蛋白代谢产生有利影响并抑制动脉粥样硬化的机制尚不确定。对血液单核细胞和培养的肝细胞的研究表明，某些大豆肽（即7S球蛋白）可刺激低密度脂蛋白（LDL）受体的表达。此途径代表了一种可能介导大豆降胆固醇和抗动脉粥样硬化作用的假设机制。然而，缺乏支持这一假设的直接证据。为了解决这一问题，我们在两种动脉粥样硬化基因工程小鼠模型中比较了膳食大豆分离蛋白的作用。一种小鼠[LDL受体-/-+载脂蛋白（apo）B转基因]缺乏LDL受体并过量产生载脂蛋白B，而另一种（apoE-/-）具有正常的LDL受体补充但不产生载脂蛋白E。研究了雄性（每组n=10-12）和去卵巢雌性（每组n=10-12）小鼠。有三个治疗组，主要区别在于饮食中蛋白质成分的来源：1）酪蛋白/乳白蛋白（无异黄酮），2）乙醇洗涤大豆分离蛋白（总异黄酮=0.04mg/g），3）完整大豆分离蛋白（总异黄酮=1.72mg/g）。通过量化主动脉中酯化胆固醇的含量来评估动脉粥样硬化。在LDL受体-/-和apoE-/-小鼠中，乙醇洗涤大豆分离蛋白（45%和31%）（P<0.05）和完整大豆分离蛋白（65%和41%）（P<0.05）均抑制了动脉粥样硬化（相对于酪蛋白/乳白蛋白组）。无性别差异。在双向分析中，大豆分离蛋白类型和小鼠类型有显著影响。LDL受体-/-小鼠的抗动脉粥样硬化作用增强（P<0.001），而喂食乙醇洗涤大豆分离蛋白的小鼠作用减弱（P<0.001）。此外，大豆对动脉粥样硬化的抑制作用与血浆LDL、极低密度脂蛋白（VLDL）或高密度脂蛋白（HDL）胆固醇浓度无关。这些结果代表了膳食大豆分离蛋白通过不依赖LDL受体和血浆脂蛋白的途径抑制动脉粥样硬化的直接证据。
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