Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Fukuoka 812-8581, Japan.
Br J Nutr. 2010 Feb;103(3):309-13. doi: 10.1017/S0007114509991814. Epub 2009 Sep 4.
Most of the investigations for an alternative medicinal treatment on atherosclerosis have been focused on natural or dietary compounds including phytochemicals. So far, few studies regarding anti-atherosclerotic small peptides except for tetrapeptide of Lys-Arg-Glu-Ser have been reported. The present study was, thus, to investigate whether dipeptide Trp-His, which is one of vasodilating small peptides, could reduce atherosclerotic lesions in apo E-deficient mice fed a high-fat diet. The animal study involved a 9-week-successive administration of Trp-His at a dose of 0, 10 or 100 mg/kg per d. After 9-week administration, en face analyses provided the first direct evidence that the atherosclerotic lesion area was significantly reduced by 27 and 38 % for Trp-His dosed at 10 and 100 mg/kg per d, respectively, compared with the control group. Administration of Trp-His did not affect growth parameters such as body weight and feeding efficiency (P>0.1). Total serum cholesterol and HDL-cholesterol as well as lipid profiles in the liver did not differ between the tested groups. Taken together, the anti-atherosclerotic effect of dipeptide Trp-His should be addressed into physiological functions of bioactive peptides, in which the dipeptide may elicit the power by alternative mechanism(s), not by the regulation of lipid metabolism.
大多数替代医学治疗动脉粥样硬化的研究都集中在天然或饮食化合物上，包括植物化学物质。到目前为止，除了赖氨酸-精氨酸-谷氨酸-丝氨酸四肽外，很少有关于抗动脉粥样硬化小肽的研究。因此，本研究旨在探讨血管扩张性小肽之一色氨酰-组氨酸二肽是否可以减少高脂饮食喂养的载脂蛋白 E 缺乏小鼠的动脉粥样硬化病变。动物研究涉及连续 9 周以 0、10 或 100 mg/kg/d 的剂量给予色氨酰-组氨酸。经过 9 周的给药后，正面分析首次提供了直接证据，表明与对照组相比，10 和 100 mg/kg/d 的色氨酰-组氨酸剂量分别使动脉粥样硬化病变面积显著减少了 27%和 38%。色氨酰-组氨酸的给药不影响体重和进食效率等生长参数（P>0.1）。各组之间的总血清胆固醇和高密度脂蛋白胆固醇以及肝脏中的脂质谱没有差异。总之，二肽色氨酰-组氨酸的抗动脉粥样硬化作用应该涉及生物活性肽的生理功能，其中二肽可能通过替代机制（而不是通过脂质代谢的调节）发挥作用。
