Aliskiren单用及联用氟伐他汀对动脉粥样硬化斑块稳定性的影响  

Effects of Aliskiren Alone and in Combination with Fluvastatin on the Stability of Atherosclerotic Plaque

作　　者：吴宏宪 成宪武[2] 马元吉 Murohara Toyoaki 钱菊英 葛均波 WU Hong-xian;CHENG Xian-wu;MA Yuan-ji;Murohara Toyoaki;QIAN Ju-ying;GE Jun-bo(Department of Cardiology,Zhongshan Hospital,Fudan Uni versify Shanghai Institute of Cardio vascular Diseases,Shanghai,200032,China;Department of Cardiologyf Nagoya University Graduate School of Medicine,Nagoya,466-8550,Japan)

机构地区：[1]复旦大学附属中山医院心内科,上海市心血管病研究所,上海200032 [2]名古屋大学医学部循环器内科学,日本名古屋466-8550

出　　处：《现代生物医学进展》2019年第12期2201-2206,共6页Progress in Modern Biomedicine

基　　金：国家重点研究发展计划项目(2016YFC1301200);国家自然科学基金项目(81800380);复旦大学附属中山医院青年基金项目(2018ZSQN03)

摘　　要：目的:观察和比较肾素抑制剂aliskiren单用或与氟伐他汀(fluvastatin)联用对动脉粥样硬化斑块稳定性的影响。方法:选择4周龄雄性ApoE-/-小鼠通过喂以高脂饮食8周建立动脉粥样硬化模型,将其随机分为5组:模型对照组、aliskiren组、肼屈嗪组、氟伐他汀组、aliskiren与氟伐他汀联合用药组,所有组别均治疗12周。取主动脉根部组织评估斑块面积(HE染色)、斑块内新生血管数量(CD31染色)及斑块稳定性指标(胶原蛋白染色、弹力纤维染色、Mac-3染色、MCP-1染色)。结果:与模型对照组比较,aliskiren单用显著降低动脉粥样硬化斑块面积,减少斑块内新生血管数量以及巨噬细胞浸润、炎症因子表达,增加斑块内弹力纤维及胶原蛋白含量(P<0.05或P<0.01)。与aliskiren单用组比较,aliskiren与氟伐他汀联用进一步降低斑块面积,改善斑块的稳定性(P<0.05或P<0.01)。与aliskiren组比较,肼屈嗪组降压幅度相似(P>0.05)。与模型对照组比较,肼屈嗪没有明显抑制斑块进展以及改善斑块的稳定性(P>0.05)。结论:Aliskiren能够抑制动脉粥样硬化斑块的进展,减少斑块内新生血管形成,改善斑块的稳定性,而其与氟伐他汀联用的治疗效果更佳。Objective: To investigate the effects of renin inhibitor aliskiren alone or in combination with fluvastatin on the stability of atherosclerotic plaque. Methods: Four-wk-old ApoE-/-mice were fed a high-fat diet until 12 weeks, and the mice were randomly assigned to one of five groups, including model group, hydralazine group, aliskiren group, fluvastatin group, aliskiren and fluvastatin combined group, for an additional 12 weeks. Plaque area(HE staining), number of neovascularization(CD31 staining) and plaque stability(collagen staining, elastic fiber staining, Mac-3 staining and MCP-1 staining) were assessed from aortic root tissue. Results: Compared with the model control group, aliskiren alone significantly reduced atherosclerotic plaque area, decreased the number of neovascularization(CD31 staining), macrophage infiltration and expression of inflammatory factors(MCP-1 staining), and increased the content of elastic fibers and collagen in the plaque(P<0.05 or P<0.01). Compared with aliskiren group, aliskiren combined with fluvastatin group further decreased the plaque area and improved the stability of atherosclerotic plaque(P<0.05 or P<0.01). Compared with aliskiren group, hydralazine group had a similar extent of lowering systolic blood pressure(P>0.05). Compared with model control group, hydralazine did not significantly inhibit plaque progression or improve plaque stability(P>0.05). Conclusions: Aliskiren can inhibit the development of atherosclerotic plaque, reduce plaque neovessel formation and improve the stability of atherosclerotic plaque. Combination of aliskiren and fluvastatin may have a better therapeutic effect in atherosclerosis-based diseases.

关 键 词：肾素抑制剂 ALISKIREN 动脉粥样硬化 氟伐他汀 血管新生 斑块稳定性 

分 类 号：R-33[医药卫生] R543.5