艾赛布考抑制兔动脉粥样硬化的作用及可能机制

Effect and Possible Mechanism of Elsibucol Inhibiting Atherosclerosis in Experimental Rabbits

目的:艾赛布考是普罗布考代谢稳定的衍生物,具有抗氧化、抗炎、抗增殖特性。本研究旨在探讨艾赛布考对高胆固醇血症兔腹主动脉损伤后动脉粥样硬化发展的影响。方法:45只雄性新西兰兔随机分为对照组、艾赛布考组、普罗布考组3组,每组15只,分别给予高脂饮食(对照组),高脂饮食+1%艾赛布考(艾赛布考组)或1%普罗布考(普罗布考组),2周后,行腹主动脉内膜球囊损伤术,继续药物干预10周。12周末,行血管内超声评价三组兔腹主动脉粥样硬化斑块面积和斑块负荷;通过免疫组织化学法观察斑块内巨噬细胞的含量,免疫组织化学法、实时定量聚合酶链式反应分别检测斑块组织内炎症因子细胞间黏附分子-1、单核细胞趋化蛋白-1、基质金属蛋白酶-9蛋白及信使核糖核酸的表达。结果:与对照组相比,艾赛布考组兔血中低密度脂蛋白胆固醇及氧化应激水平显著降低,腹主动脉粥样硬化斑块内巨噬细胞含量及炎症因子表达也降低,斑块面积及斑块负荷显著减少(P均<0.01)。与普罗布考组相比,艾赛布考组兔腹主动脉斑块面积及斑块负荷降低更加显著,差异具有统计学意义(P均<0.01)。结论:艾赛布考通过调脂、抗炎、抗氧化作用,抑制内膜损伤后动脉粥样硬化进展。

Objective：Elsibucol is a metabolically stable derivative of probucol with the properties of anti-oxidation, anti-inflammation and anti-proliferation.We want to explore the effect of elsibucol on abdominal aorta injury in hypercholesterolemia rabbits. Methods： A total of 45 male New Zealand rabbits were divided into 3 groups： Control group, the rabbits were fed by high cholesterol diet, Elsibucol group, the rabbits received high cholesterol diet with 1% elsibucol and Probucol group, the rabbits received high cholesterol diet with 1% probucol. n =15 in each group. All animals were treated for 2 weeks followed by the procedure of abdominal aortic balloon injury and then, drug therapy was continued for 10 weeks. The area and load of atherosclerosis in abdominal aorta were evaluated by IVUS, the amount of macrophages in plaque were observed by immunohistochemistry, m RNA and protein expressions of MCP-1, MMP-9 were examined by RT-PCR and immunohistochemistry.Results： Compared with Control group, Elsibucol group showed decreased blood LDL-C and oxidative stress, decreased amount of macrophages and lower expression of inflammatory factors in atherosclerosis plaque, reduced plaque area and load, all P〈0.01. Compared with Probucol group, Elsibucol group presented even lower plaque area and load, all P〈0.01.Conclusion： Elsibucol inhibits the progress of atherosclerosis in experimental rabbits via regulating blood lipids, antiinflammation and anti-oxidation.