链脲佐菌素诱导的新西兰大白兔血脂组分和动脉粥样硬化病理特征

The blood lipid changes and atherosclerotic lesion in streptozotocin induced rabbit model

目的 探讨链尿佐菌素 (STZ)和饮食结构对新西兰大白兔血脂组分及动脉粥样硬化 (AS)的作用 ,以寻找方便实用的动物模型。方法 比较STZ和高胆固醇饲料对新西兰大白兔血脂组分和AS病变的作用 ,并分析AS病变局部清道夫受体A(SRA)表达与泡沫细胞分布的关系。结果 STZ可致动物血甘油三酯 (TG)轻 中度升高、HDL C降低及大动脉AS病变 ,高胆固醇饲料显著增加各种脂蛋白颗粒的胆固醇含量 ,并能加速AS发生发展。STZ所致的血脂紊乱与大多数冠心病患者相似 ,其AS病变局部的泡沫细胞绝大多数来源于单核巨噬细胞 ,清道夫受体A基因及蛋白质表达与巨噬细胞分布相同 ,其表达量与AS病变程度一致。STZ造成的胰岛素分泌相对或绝对不足及apoCⅢ分泌增加可能高TG血症的重要原因。

Objective To compare the effects of streptozotocin and diet structure on the blood lipid contents and atherosclerotic lesions in the New Zealand white (NZW) rabbit. Methods The blood lipid and atheroma in rabbits treated with streptozotocin and/or fed high cholesterol diets were compared, the association between scavenger receptor A expression and monocyte macrophage and foam cells distribution were analyzed. Results The slight decreased blood HDL C?the moderate increased TG levels and large artery atheroma were in the NZW rabbits treated with streptozotocin and fed with normal chow. High cholesterol diet remarkably augmented the cholesterol contents of the various lipoprotein particles ,and could speed up arteriosclerotic plaque development. The dyslipidemia of this animal model was similar to most of the clinical patients with coronary heart disease, most of the foam cells in the atheroma came from monocyte macrophage cells in this animal model. Scavenger receptor A mRNA and protein expressions were detected only in macrophage derived foam cells in both early and advanced atherosclerotic lesions. The high blood TG levels could be related with low insulin and high apoCⅢ secretion induced by streptozotocin. Conclusion Rabbits treated with streptozotocin and fed with normal chow is a suitable model for studying hypertriglyceridemia and atheroma.