Jagiellonian University School of Medicine, Cracow, Poland.
Med Sci Monit. 2012 Oct;18(10):BR389-93. doi: 10.12659/msm.883478.
The aim of this study was to investigate whether the 3 different substances that can decrease the development of atherosclerosis--nebivolol, AVE 0991 and doxycycline--could at the same time diminish the level of inflammatory indicators interleukin-6 (IL-6), interleukin-12 (IL-12), serum amyloid A (SAA), and monocyte chemotactic protein-1 (MCP-1).
MATERIAL/METHODS: Forty 8-week-old female apoE-knockout mice on the C57BL/6J background were divided into 4 groups and put on chow diet for 4 months. Three experimental groups received the same diet as a control group, mixed with AVE 0991 at a dose 0.58 µmol per kg of body weight per day, nebivolol at a dose 2.0 µmol per kg of body weight per day, and doxycycline at a dose 1.5 mg per kg of body weight per day. At the age of 6 months, the mice were sacrificed.
All inflammatory indicators (MCP-1, IL-6, IL-12 and SAA) were diminished by AVE 0991. There was also a tendency to lower MCP-1, IL-6, IL-12 and SAA levels by nebivolol and doxycycline; however, it did not reach statistical significance.
Of the 3 presented substances, only AVE 0991 was able to diminish the rise of inflammatory markers. Therefore, drug manipulations in the renin-angiotensin-aldosterone axis seem to be the most promising in the future treatment of atherogenesis.
本研究旨在探讨 3 种能够减缓动脉粥样硬化形成的物质——奈必洛尔、AVE0991 和强力霉素是否同时能够降低炎症指标白细胞介素-6（IL-6）、白细胞介素-12（IL-12）、血清淀粉样蛋白 A（SAA）和单核细胞趋化蛋白-1（MCP-1）的水平。
材料/方法：40 只 8 周龄雌性载脂蛋白 E 基因敲除小鼠（C57BL/6J 背景）被分为 4 组，给予标准饮食，喂养 4 个月。3 个实验组给予与对照组相同的饮食，同时混合 AVE0991（0.58µmol/kg/天）、奈必洛尔（2.0µmol/kg/天）和强力霉素（1.5mg/kg/天）。在 6 个月龄时，处死小鼠。
所有炎症指标（MCP-1、IL-6、IL-12 和 SAA）均被 AVE0991 降低。奈必洛尔和强力霉素也有降低 MCP-1、IL-6、IL-12 和 SAA 水平的趋势，但未达到统计学意义。
在所研究的 3 种物质中，只有 AVE0991 能够降低炎症标志物的升高。因此，在未来治疗动脉粥样硬化形成方面，对肾素-血管紧张素-醛固酮轴的药物干预似乎最有前途。
