阿托伐他汀对动脉粥样硬化模型兔Wnt/β-连环蛋白信号通路的影响研究

Effects of Atorvastatin on the Wnt/β-catenin Signal Pathway in Atherosclerosis Model Rabbits

目的:研究阿托伐他汀对动脉粥样硬化模型兔Wnt/β-连环蛋白(β-catenin)信号通路中调控因子Wnt1、β-catenin、蓬乱蛋白1(dvl-1)的影响,探讨其作用机制。方法:取兔随机分为正常对照组、模型组(高脂饲料)、处理组(高脂饲料+阿托伐他汀2.5mg.kg-1.d-1),每组8只,各组兔给予相应饲料喂养,每日1次,12周后采血并处死,检测各组兔的血脂指标(总胆固醇、甘油三酯、低密度脂蛋白胆固醇),观察主动脉硬化斑块的程度,免疫组化法和蛋白质印迹法检测主动脉硬化斑块处Wnt1、β-catenin及dvl-1蛋白的表达情况。结果:与正常对照组比较,模型组和处理组血脂指标明显升高,主动脉硬化斑块的程度明显增强,Wnt1、β-catenin及dvl-1蛋白的表达明显增强(P<0.05);与模型组比较,处理组血脂指标明显降低,主动脉硬化斑块的程度明显减轻,Wnt1、β-catenin及dvl-1蛋白的表达明显降低(P<0.05)。结论:阿托伐他汀可能通过抑制Wnt/β-catenin信号通路中Wnt1、β-catenin及dvl-1蛋白的表达来减轻动脉粥样硬化的程度。

OBJECTIVE： To study the effects of atorvastatin on Wntl, β-catenin and dvl-1 in Wnt/β-catenin signal pathway in atherosclerosis rabbit, and to explore the possible mechanisms. METHODS： Rabbits were randomly divided into normal control group, model group （high-fat diet） and treatment group （high-fat diet＋atorvastatin 2.5 mg. kg-1. d-1） with 8 rabbits in each group. Those groups were given relevant diet once a day and then sacrificed 12 weeks later. The blood lipid index （TC, TG and LDL-C） of rabbits was determined and the degree aortic plaques were observed. The expression of Wntl, β-catenin and dvl-1 in aortic plaques was detected by immunohistochemistry and Western blot method. RESULTS： Compared with normal control group, the blood lipid index in model group and treatment group increased significantly, atherosclerotic plaque got worse significantly, and the expression of Wntl, β-catenin and dvl-1 increased significantly （P〈0.05）; compared with model group, the blood lipid index in treatment group reduced significantly, atherosclerotic plaques were relieved significantly and the expression of Wntl,β-catenin and dvl-1 decreased significantly （P〈0.05）. CONCLUSION： Atorvastatin may relieve the degree of atherosclerosis by inhibiting the expression of Wntl, β-catenin and dvl-1 in Wnt/β-catenin signal pathway.