阿利吉仑单用及联用阿托伐他汀对动脉粥样硬化小鼠炎症因子的影响

目的:考察阿利吉仑单用或与阿托伐他汀联用对动脉粥样硬化小鼠炎症因子的影响。方法:将12周龄apoE^-/-雄性小鼠给予高脂饮食,随机分为6组(n=8),包括模型对照组,肼屈嗪组、阿利吉仑低剂量组、阿利吉仑高剂量组、阿托伐他汀组、阿利吉仑与阿托伐他汀联合用药组,均治疗12周。采用酶联免疫吸附的方法(ELISA)测定血浆中白介素-6(IL-6)、C反应蛋白(CRP)和单核细胞趋化蛋白-1(MCP-1)的水平;光学显微镜下测定动脉粥样硬化病变区与总主动脉面积。结果:与模型对照组相比,阿利吉仑单独用药对炎症因子MCP-1的影响无显著性差异。阿利吉仑单独或者联合阿托伐他汀用药能够显著降低炎症介质IL-6、CRP的血浆水平(P<0.05),且阿利吉仑高、低剂量组之间对CRP和IL-6水平的影响亦有差异;阿利吉仑联用阿托伐他汀与阿托伐他汀组对MCP-1、IL-6、CRP水平的影响均无显著性差异(P>0.05)。组织病理学结果显示:单用阿利吉仑或联合应用阿托伐他汀都有不同程度的降低动脉粥样硬化面积,与模型对照组相比均有显著性差异,且单用阿利吉仑组、阿托伐他汀组均与联合用药组有显著性差异(P<0.05)。结论:阿利吉仑对动脉粥样硬化小鼠体内炎症因子水平有一定影响,并显示出一定的剂量依赖性,同时与阿托伐他汀合用有一定的联合治疗作用。

Influences of aliskiren alone and in combination with atorvastatin on inflammatory cytokines in atherosclerotic mice

OBJECTIVE To investigate anti-inflammatory effects of aliskiren alone and in combination with atorvastatin on atherosclerosis in apoE^-/- male mice. METHODS Twelve weeks old male apoE^-/- mice fed a high fat diet were randomly divided into six groups, eight mice per group. These groups included model control group, hydralazine group, low dose aliskiren group, high dose aliskiren group, atovarstatin group, aliskiren combined with atovarstatin group. Mice in each group were treated for 12 weeks. Plasma levels of interleukin-6 (IL-6), C reactive protein (CRP) and monocyte/macrophage chemotactic protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay (ELISA) methods in all animals. Atherosclerotic lesion area and total area of the aorta were determined under optical microscope. RESULTS Results showed that, compared with model control group, aliskiren alone had no effects on MCP-1, but aliskiren alone or in combination with atovarstatin could significantly reduce levels of IL-6 and CRP (P<0.05). There were some differences in CRP and IL-6 between high and low dose aliskiren groups. Meanwhile, there was no significant difference in MCP-1, CRP and IL-6 between aliskiren combination group and atovarstatin group (P>0.05). Histopathology results showed that, compared with model control group, aliskiren alone and in combination with atorvastatin could reduce atherosclerosis area to different degrees, with significant differences between different groups. There were significant differences between aliskiren alone group/atorvastatin group and combination group (P<0.05). CONCLUSION Aliskiren has some effects on inflammatory cytokines in atherosclerotic mice in a dose dependent manner. Combination with atorvastatin has certain synergistic effects.