Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
Exp Mol Med. 2012 May 31;44(5):311-8. doi: 10.3858/emm.2012.44.5.035.
In this study, the synergistic effect of 6-[4-(1-cyclohexyl- 1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H )-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.
在这项研究中,我们研究了 6-[4-(1-环己基-1H-四唑-5-基)丁氧基]-3,4-二氢-2(1H)-喹啉酮(西洛他唑)和银杏叶提取物(GbE)在载脂蛋白 E(ApoE)基因敲除小鼠中的协同作用。GbE 和西洛他唑联合治疗可协同减少高脂饮食喂养的 ApoE 基因敲除小鼠的活性氧(ROS)产生。与未治疗的 ApoE 小鼠相比,联合治疗可显著减少动脉粥样硬化病变面积。炎性细胞因子和黏附分子如单核细胞趋化蛋白-1(MCP-1)、可溶性血管细胞黏附分子-1(sVCAM-1)和 VCAM-1 可引发动脉粥样硬化,GbE 与西洛他唑的联合治疗可显著降低这些分子的水平。此外,联合治疗还可减少巨噬细胞向内膜的浸润。这些结果表明,GbE 与西洛他唑联合治疗在高脂血症 ApoE 基因敲除小鼠中比单独使用西洛他唑具有更强的抗动脉粥样硬化作用,可能是治疗动脉粥样硬化的一种有价值的治疗策略。