Bell F P, Schaub R G
Metabolic Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Exp Mol Pathol. 1989 Jun;50(3):327-36. doi: 10.1016/0014-4800(89)90042-7.
New Zealand rabbits (six each) were either maintained on a standard chow diet (ND) or the chow diet supplemented with cholesterol/peanut oil (HD) for 2 weeks. After 2 weeks, each animal had 15 ml of a 1% carrageenan gel injected subcutaneously into the midabdominal area. Rabbits were maintained on the diets for an additional 4 weeks. At sacrifice, blood was collected both for serum and for monocyte isolation and granulomas and aorta were excised. Tissues were assayed for lipid composition and lipid metabolism. Electron and light microscopies were performed on granuloma tissue. Granulomas from ND animals did not stain with oil red O. Granulomas from HD animals had homogenous oil red O staining indicating lipid accumulation. Granulomas from both ND and HD animals consisted of macrophages. Macrophages from ND rabbits accumulated follicular carrageenan but not lipid, while HD macrophages had the appearance of foam cells. Granuloma lipid content and metabolism closely paralleled the aorta and blood monocytes. The HD tissue had increased acylCoA:cholesterol acetyltransferase (ACAT) activity and lipid composition changes reflective of the atherosclerotic process. ND granulomas had no elevation of lipid content or ACAT. The carrageenan-induced granulomas provide a useful model for studying the biochemical and morphologic changes characteristic of arteries undergoing atherogenic change.
新西兰兔(每组6只)分别给予标准饲料(正常饮食组,ND)或添加胆固醇/花生油的饲料(高脂饮食组,HD),持续2周。2周后,每只动物在腹部中部皮下注射15毫升1%的角叉菜胶凝胶。兔子继续按原饮食喂养4周。处死时,采集血液用于血清和单核细胞分离,切除肉芽肿和主动脉。对组织进行脂质成分和脂质代谢分析。对肉芽肿组织进行电子显微镜和光学显微镜检查。正常饮食组动物的肉芽肿不被油红O染色。高脂饮食组动物的肉芽肿有均匀的油红O染色,表明有脂质蓄积。正常饮食组和高脂饮食组动物的肉芽肿均由巨噬细胞组成。正常饮食组兔子的巨噬细胞积聚滤泡角叉菜胶但不积聚脂质,而高脂饮食组的巨噬细胞呈泡沫细胞外观。肉芽肿脂质含量和代谢与主动脉和血液单核细胞密切平行。高脂饮食组组织中酰基辅酶A:胆固醇乙酰转移酶(ACAT)活性增加,脂质成分变化反映了动脉粥样硬化过程。正常饮食组肉芽肿脂质含量或ACAT无升高。角叉菜胶诱导的肉芽肿为研究动脉粥样硬化性改变特征的生化和形态学变化提供了一个有用的模型。