Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama, 700-8558, Japan.
Transl Stroke Res. 2012 Dec;3(4):435-41. doi: 10.1007/s12975-012-0198-1. Epub 2012 Jul 21.
To investigate the effects of amlodipine in combination with atorvastatin on carotid atherosclerotic changes in metabolic syndrome, 8-week-old Zucker fatty rats were treated with vehicle, amlodipine, atorvastatin, or amlodipine in combination with atorvastatin for 28 days. Histological studies of common carotid arteries showed that lipid deposition determined by Sudan III staining was significantly reduced in rats treated with amlodipine or atorvastatin alone and was further reduced by amlodipine in combination with atorvastatin. Immunohistochemical studies of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, the arterial calcification initiator bone morphogenetic protein (BMP) 2, the angiogenic factor Notch1, and the smooth muscle cell marker α-smooth muscle actin (SMA) showed that the high expression of all four protein in vehicle-treated rats was greatly decreased by amlodipine, atorvastatin, or amlodipine in combination with atorvastatin, in ascending order. Double immunostaining showed marked colocalization of TNF-α with bone morphogenetic protein 2 and Notch1 with α-SMA in the vehicle group, which was greatly reduced by amlodipine plus atorvastatin. These data suggest that combination therapy may be more effective in preventing atherosclerotic processes and subsequent carotid vascular events than administrating amlodipine or atorvastatin alone in metabolic syndrome.
为了研究氨氯地平联合阿托伐他汀对代谢综合征颈动脉粥样硬化变化的影响，将 8 周龄的 Zucker 肥胖大鼠用 vehicle（赋形剂）、氨氯地平、阿托伐他汀或氨氯地平联合阿托伐他汀处理 28 天。颈总动脉的组织学研究表明，苏丹 III 染色测定的脂质沉积在单独使用氨氯地平和阿托伐他汀的大鼠中明显减少，而氨氯地平联合阿托伐他汀进一步减少。对促炎细胞因子肿瘤坏死因子（TNF）-α、动脉钙化启动子骨形态发生蛋白（BMP）2、血管生成因子 Notch1 和平滑肌细胞标记物α-平滑肌肌动蛋白（α-SMA）的免疫组织化学研究表明，在 vehicle 处理的大鼠中，这四种蛋白的高表达均被氨氯地平、阿托伐他汀或氨氯地平联合阿托伐他汀显著降低，依次递增。双重免疫染色显示，在 vehicle 组中，TNF-α 与骨形态发生蛋白 2 以及 Notch1 与α-SMA 明显共定位，而氨氯地平联合阿托伐他汀可显著减少这种共定位。这些数据表明，与单独使用氨氯地平或阿托伐他汀相比，联合治疗可能更有效地预防代谢综合征中的动脉粥样硬化过程和随后的颈动脉血管事件。
