豚鼠早期动脉粥样硬化模型的建立、机制研究及与大鼠模型的比较  

The establishment and evaluation of early atherosclerosis models in guinea pigs and rats

作　　者：杨润梅[1] 李金莲[1] 高南南[1] 陈慧敏[1] 蔡大勇[1] 屠宴会[1] 

机构地区：[1]中国医学科学院药用植物研究所药理毒理研究中心,北京100193

出　　处：《中国药理学通报》2011年第2期285-289,共5页Chinese Pharmacological Bulletin

基　　金：国家科技部"重大新药创制"科技重大专项-综合性新药研究开发技术大平台-创新药物研究开发技术平台建设(No2009ZX09301-003)

摘　　要：目的建立豚鼠早期动脉粥样硬化模型,探讨模型形成机制,并与大鼠模型进行比较,为豚鼠模型优势提供科学依据。方法应用高脂饲料诱导法,观察豚鼠和大鼠是否可形成早期动脉粥样硬化模型,并应用免疫组化和酶联免疫分析技术探讨模型形成机制。结果豚鼠模型组摄入高脂饲料6周后主动脉内膜-中膜明显增厚、内膜单核细胞、巨噬细胞浸润与聚集增多,同时比例为0.40的动物动脉内膜表层进一步发展形成脂纹脂斑病变。而大鼠模型组未见类似病变。机制研究表明,血清脂蛋白(a)[Lipoprotein(a),LP(a)]、胆固醇酯转运蛋白(Cholesteryl ester transfer protein,CETP)、氧化型低密度脂蛋白(ox-LDL)浓度,肝脏脂酰辅酶A:胆固醇酰基转移酶(Acyl-CoA:cholesterol acyltransferase,ACAT)活性和主动脉增殖细胞核抗原(Proliferating cell nu-clear antigen,PCNA)、分化抗原簇-36(Cluster of differentiation36,CD36)和血管细胞黏附分子(Vascular cell adhesion mole-cule,VCAM-1)表达的变化是动脉病理改变的重要机制。结论豚鼠可能是一种模拟早期动脉粥样硬化的适宜动物模型。Aim To build up the model of early atherosclerosis in guinea pig and rats and to compare the differences in mechanisms underlying the development of atherosclerosis between the two species.Methods Whether the guinea pig and the rat can develop early atherosclerosis with high lipid diets was investigated,and the mechanisms were explored by immunohistochemistry and enzyme-linked immunoassay.Results After fed with high fat diet for 6 weeks,the serum TC and LDL-C level increased,the aortic aortic intima-media area significantly thickened,and the infiltration and aggregation of monocytes of intima and macrophages significantly increased in guinea pigs.In addition,40 percent of the arterial intimal surface developed into fatty streak formation of plaque lesions.But such changes were not observed in rats.The mechanisms involved the arterial pathology included the change of lipoprotein（a）,cholesteryl ester transfer protein（CETP）,ox-LDL concentration,acyl-CoA：cholesterol acyltransferase（ACAT）activity,proliferating cell nuclear antigen（PCNA）,cluster of differentiation 36（CD36）and vascular cell adhesion molecule（VCAM-1）expressions.Conclusion A guinea pig model is suitable for simulating the early stage of atherosclerosis.

关 键 词：豚鼠 早期动脉粥样硬化 酯酰辅酶A:胆固醇酰基转移酶(ACAT) 胆固醇酯转移蛋白(CETP) 脂蛋白(a)[LP(a)] 细胞分化抗原36(CD36) 血管细胞黏附分子(VCAM-1) 增殖细胞核抗原(PCNA) 

分 类 号：R-332[医药卫生] R322.121