Hayashi Toshio, Sumi Daigo, Matsui-Hirai Hisako, Fukatsu Akiko, Arockia Rani P Juliet, Kano Hatsuyo, Tsunekawa Taku, Iguchi Akihisa
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Japan.
Atherosclerosis. 2003 May;168(1):23-31. doi: 10.1016/s0021-9150(03)00054-6.
Although sarpogrelate HCl is widely used for the prevention of arterial thrombosis, its effect on atherosclerosis is unknown. Accordingly, we here investigated the effects of sarpogrelate HCl on a rabbit model of atherosclerosis. Male rabbits were fed a 0.5% cholesterol diet (HCD) (Gp 1), HCD with vitamin E (Gp 2), HCD with vitamin E and sarpogrelate (Gp 3), or HCD with sarpogrelate alone (Gp 4) for 8 weeks. The atherosclerotic area was decreased by feeding of vitamin E and sarpogrelate (16.9+/-2.0% in Gp 1 vs. 8.2+/-2.0% in Gp 3). Tone-related basal NO release was higher in Gps 3 and 4. Acetylcholine-induced relaxation tended to be improved in Gp 3. The amount of eNOS mRNA was increased in Gp 4, and aortic cyclic GMP concentration showed the same tendency. O(2)(-) release tended to be decreased in Gps 2 and 3. The matrix metalloproteinase-1 (MMP-1)-positive area was decreased, and the percentage ratio of cell numbers of smooth muscle cells/macrophages in the plaque was increased in Gp 3. The results demonstrated that sarpogrelate HCl retards the progression of atherosclerosis in rabbits, and that this effect is enhanced by concomitant administration of vitamin E. Although upregulation of eNOS may play a role as one of the underlying mechanisms, our results suggest that an additional mechanism-possibly involving the antiproliferative effects of sarpogrelate HCl on smooth muscle cells and macrophages-may also play an important role.
尽管盐酸沙格雷酯被广泛用于预防动脉血栓形成，但其对动脉粥样硬化的影响尚不清楚。因此，我们在此研究了盐酸沙格雷酯对兔动脉粥样硬化模型的影响。雄性兔被喂食0.5%胆固醇饮食（高胆固醇饮食，Gp 1）、含维生素E的高胆固醇饮食（Gp 2）、含维生素E和沙格雷酯的高胆固醇饮食（Gp 3）或仅含沙格雷酯的高胆固醇饮食（Gp 4），持续8周。喂食维生素E和沙格雷酯可使动脉粥样硬化面积减小（Gp 1为16.9±2.0%，Gp 3为8.2±2.0%）。Gp 3和Gp 4中与张力相关的基础一氧化氮释放较高。Gp 3中乙酰胆碱诱导的舒张趋于改善。Gp 4中内皮型一氧化氮合酶（eNOS）mRNA的量增加，主动脉环磷酸鸟苷（cGMP）浓度呈现相同趋势。Gp 2和Gp 3中氧阴离子（O₂⁻）释放趋于减少。Gp 3中基质金属蛋白酶-1（MMP-1）阳性面积减小，斑块中平滑肌细胞/巨噬细胞的细胞数百分比增加。结果表明，盐酸沙格雷酯可延缓兔动脉粥样硬化的进展，且维生素E的联合给药可增强这种作用。尽管eNOS的上调可能作为潜在机制之一发挥作用，但我们的结果表明，另一种机制——可能涉及盐酸沙格雷酯对平滑肌细胞和巨噬细胞的抗增殖作用——也可能起重要作用。
