阿托伐他汀联用依折麦布对新西兰兔动脉粥样硬化的影响

目的探讨阿托伐他汀联用依折麦布对新西兰白兔动脉粥样硬化的影响。方法将32只雄性新西兰白兔随机分为4组:对照组、模型组、阿托伐他汀干预组和联合药物干预组,每组8只,分别给予普通饲料、高胆固醇饲料、高胆固醇饲料+阿托伐他汀5 mg·kg~(-1)·d~(-1)、高胆固醇饲料+阿托伐他汀5 mg·kg~(-1)·d~(-1)+依折麦布1l mg·kg~(-1)·d~(-1)处理。12周后,酶法检测血清甘油三酯、胆固醇、HDL-C和LDL-C;HE染色观察动脉和肝脏病理形态学改变;高效液相色谱法检测动脉壁胆固醇含量;Western blot检测肝脏pcsk9和动脉壁CD36蛋白表达。结果与模型组比较,阿托伐他汀干预组和联合药物干预组甘油三酯、胆固醇、LDL-C明显下降(P<0.05,p<0.01);与阿托伐他汀干预组比较,联合药物干预组血清胆固醇和LDL-C水平明显下降(P<0.05),pcsk9和动脉壁CD36蛋白表达明显下降(P<0.05),但在动脉壁内膜病变减轻程度上,两组无明显差异。结论阿托伐他汀与依折麦布联用可能通过影响CD36和pcsk9表达,发挥更好地调脂、消斑、改善动脉壁和肝脏功能的作用。

Effects of coadministration of atorvastatin with ezetimibe on atherosclerosis in New Zealand white rabbits

Objective To investigate the effects of coadministration of atorvastatin with ezetimibe on atherosclerosis in New Zealand white rabbits. Methods Thirty-two male New Zealand white rabbits were randomly divided into 4 groups: control group (n = 8),model group (n = 8),atorvastatin treatment group (n = 8) and coadministration group (n = 8) ,and respectively treated with normal diet,high cholesterol diet,high cholesterol diet+atorvastatin 5 mg·kg~(-1)·d~(-1), and high cholesterol diet+atorvastatin 5 mg·kg~(-1)·d~(-1)+ezetimibe 1 mg·kg~(-1)·d~(-1) for 12 weeks. Serum lipid level(TG,TC, HDL-C and LDL-C) was measured by enzymatic method. Lesions of arteries and liver were observed after hematoxylin-eosin staining. The content of cholesterol in arterial wall was quantitated by high performance liquid chromatography. The expression of liver pcsk9 and arterial wall CD36 protein was determined by Western blotting. Results Compared with atorvastatin treatment group,the coadministration of atorvastatin with ezetimibe could better decrease the level of serum TC and LDL-C,inhibit the cholesterol accumulation in arterial wall, down-regu-late the expression of liver pcsk9 and arterial wall CD36 protein,improve the liver fatty degeneration. However,there was no significant difference in reversing atherosclerosis between atorvastatin group and coadministration group. Conclusion The coadministration of atorvastatin with ezetimibe may play better role in lowering lipid, reversing plaque and improving the functions of artery and liver through influencing expression of pcsk9 and CD36.