Takase Hiromichi, Hashimoto Ayako, Okutsu Reiko, Hirose Yoshimi, Ito Hideki, Imaizumi Takashi, Miyakoda Goro, Mori Toyoki
Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
Arzneimittelforschung. 2007;57(4):185-91. doi: 10.1055/s-0031-1296604.
To investigate whether cilostazol (CAS 73963-72-1), a selective phosphodiesterase 3 inhibitor, reduces the progression of atherogenic diet-induced atherosclerosis, cilostazol was orally administered twice a day for 4 weeks to male apolipoprotein-E knockout (ApoE KO) mice. In serial sections of the aortic root, the atherosclerotic lesion ratios in the cilostazol-treated groups (32.5 +/- 3.3% for 100 mg/kg, 29.0 +/- 2.9% for 300 mg/kg) were significantly and dose-dependently smaller than that of the control group (40.2 +/- 3.7%). Cilostazol also significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte/macrophage accumulation in the aortic root and increased high-density lipoprotein(HDL) cholesterol levels in plasma. These results suggest that cilostazol suppresses the progression of atherosclerosis in ApoE KO mice by inhibiting adhesionand infiltration of monocytes and reducing cholesterol accumulation in atherosclerotic lesion.
为研究选择性磷酸二酯酶3抑制剂西洛他唑（CAS 73963-72-1）是否能减缓致动脉粥样化饮食诱导的动脉粥样硬化进展，对雄性载脂蛋白E基因敲除（ApoE KO）小鼠每日口服西洛他唑两次，持续4周。在主动脉根部的连续切片中，西洛他唑治疗组（100 mg/kg剂量组为32.5 +/- 3.3%，300 mg/kg剂量组为29.0 +/- 2.9%）的动脉粥样硬化病变比例显著低于对照组（40.2 +/- 3.7%），且呈剂量依赖性。西洛他唑还显著降低了主动脉根部血管细胞黏附分子-1（VCAM-1）的表达以及单核细胞/巨噬细胞的聚集，并提高了血浆中高密度脂蛋白（HDL）胆固醇水平。这些结果表明，西洛他唑通过抑制单核细胞的黏附和浸润以及减少动脉粥样硬化病变中的胆固醇积聚，从而抑制ApoE KO小鼠的动脉粥样硬化进展
