Amy R M, Dolphin P J, Pederson R A, Russell J C
Department of Pathology, University of Alberta, Edmonton, Canada.
Atherosclerosis. 1988 Feb;69(2-3):199-209. doi: 10.1016/0021-9150(88)90015-9.
Two strains of obese rats, the fatty Zucker and the LA/N-corpulent have been compared at 6 months age for the presence of vascular and myocardial disease. Both strains, when obese, exhibit a VLDL hyperlipidemia with elevated triglycerides and moderate elevations of plasma cholesterol concentrations compared to the lean rats of the same strain. The hyperlipidemia is more modest in the fatty Zucker than the corpulent LA/N, and the serum lipid concentrations of the lean Zucker are lower than those of the lean LA/N. Apolipoprotein concentrations were similar and elevated in the two obese genotypes compared to the lean genotypes which were also similar to each other. Male and female obese animals of both strains exhibited hyperinsulinemia under fasting conditions and after oral glucose, with obese male LA/N rats exhibiting the most severe hyperinsulinemia. Glucose tolerance was impaired in obese LA/N animals but was normal in lean rats of both strains and fatty Zucker rats of both sexes. The glucose intolerance observed in obese LA/N animals was more severe in the male than in the female rats. Unlike the corpulent rat, which develops atherosclerotic lesions, the fatty Zucker shows no evidence of advanced vascular lesions on scanning electron microscopy. The fatty Zucker also does not develop the myocardial lesions that are frequent in the male corpulent LA/N rat. It is suggested that the initiation of the atherogenic process is dependent upon elevated insulin levels or transient hyperglycemia. Development of the advanced lesions appears to require the presence of hyperlipidemia.
在6月龄时,对两种肥胖大鼠品系,即肥胖型 Zucker 大鼠和 LA/N-肥胖大鼠,进行了血管和心肌疾病方面的比较。与同品系的瘦大鼠相比,这两种品系的大鼠在肥胖时均表现出极低密度脂蛋白(VLDL)高脂血症,甘油三酯升高,血浆胆固醇浓度中度升高。肥胖型 Zucker 大鼠的高脂血症比肥胖的 LA/N 大鼠更为轻微,瘦 Zucker 大鼠的血脂浓度低于瘦 LA/N 大鼠。与彼此也相似的瘦基因型相比,两种肥胖基因型的载脂蛋白浓度相似且升高。两种品系的肥胖雄性和雌性动物在禁食条件下和口服葡萄糖后均表现出高胰岛素血症,肥胖雄性 LA/N 大鼠表现出最严重的高胰岛素血症。肥胖的 LA/N 动物葡萄糖耐量受损,但两种品系的瘦大鼠和两性的肥胖型 Zucker 大鼠葡萄糖耐量正常。肥胖的 LA/N 动物中观察到的葡萄糖不耐受在雄性大鼠中比雌性大鼠更严重。与会发生动脉粥样硬化病变的肥胖大鼠不同,肥胖型 Zucker 大鼠在扫描电子显微镜下未显示出晚期血管病变的迹象。肥胖型 Zucker 大鼠也不会发生在肥胖雄性 LA/N 大鼠中常见的心肌病变。有人提出,动脉粥样硬化过程的起始取决于胰岛素水平升高或短暂性高血糖。晚期病变的发展似乎需要高脂血症的存在。