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目的研究阿托伐他汀对动脉粥样硬化家兔主动脉斑块的影响及其可能的机制。方法 18只雄性日本大耳白兔随机分为3组:普通饲料组、高脂饲料组、高脂饲料+阿托伐他汀组,每组各6只。喂养16周后,采集各组家兔血清、主动脉及肝脏。检测各组家兔血清中血脂水平及主动脉病变的变化;提取各组胸主动脉及肝脏组织总RNA;实时定量PCR检测各组织内内脏脂肪素(Visfatin)、沉默信息调节因子1(Sirt1)、Bcl-2、C-myc及P53的mRNA水平变化。结果和对照组相比,高脂组和阿托伐他汀组家兔TC、LDL-C升高(t值分别为47.535、12.011,P值均为0),但阿托伐他汀组较高脂喂养家兔的血胆固醇(TC)和低密度脂蛋白(LDL-C)显著降低(t值分别为10.245、11.765;P值均<0.001);与高脂组相比,阿托伐他汀组家兔主动脉visfatin的mRNA水平下降(t=10.327,P<0.001),Bcl-2水平升高(t=7.042,P=0.001),肝脏组织中visfatin和p53的mRNA水平下降(t值分别为6.735,6.452;P=0.001),sirt1mRNA水平升高(t=8.328,P=0.001)。结论阿托伐他汀能够降低高血脂水平和抑制动脉粥样硬化,机制可能与降低Visfatin,p53表达及促进Sirt1,Bcl-2表达有关。
Objective To study the effect of atorvastatin on aortic plaque in atherosclerotic rabbits and its possible mechanism. Methods Eighteen male Japanese white rabbits were randomly divided into three groups: normal diet group, high fat diet group, high fat diet + atorvastatin group, 6 in each group. After 16 weeks of feeding, serum, aorta and liver of rabbits in each group were collected. The serum levels of lipids and the changes of the aortic lesions in each group were detected. The total RNA was extracted from the thoracic aorta and liver of each group. The levels of Visfatin, Sirt1, , Bcl-2, C-myc and P53 mRNA levels. Results Compared with the control group, the levels of TC and LDL-C in high-fat group and atorvastatin group were significantly higher (t = 47.535 and 12.011, respectively, P = 0) Blood cholesterol (TC) and low density lipoprotein (LDL-C) were significantly decreased in fed rabbits (t = 10.245 and 11.765, respectively; all P values <0.001). Compared with hyperlipidemia group, The levels of visfatin and p53 mRNA in the aorta of rabbits decreased (t = 10.327, P <0.001) and the levels of Bcl-2 increased (t = 7.042, P = 0.001) , 6.452; P = 0.001), sirt1 mRNA levels increased (t = 8.328, P = 0.001). Conclusions Atorvastatin can reduce hyperlipidemia and inhibit atherosclerosis, which may be related to the decrease of Visfatin and p53 expression and the expression of Sirt1 and Bcl-2.