Development of animal model of hyperlipidemia related to evolution of coronary artery disease.

我们从WHHL（Watanabe遗传性高脂血症）兔中分离出两个具有高和低水平高脂血症的品系。在血浆甘油三酯水平上重复选择的近亲繁殖。低水平（甘油三酯<500 mg/dl ; TGL组）和高水平（甘油三酯>= 500 mg/dl ; TGH组）高甘油三酯血症的外显率在第4代分别为100%和90%。TGL<plus-minus><plus-minus><plus-minus>组（9-10月龄）和TGH组（9-10月龄）血浆总胆固醇和甘油三酯分别为719 ~ 131（平均SD）和241 ~ 69 mg/dl<plus-minus>，与TGL<plus-minus>组相比有显著性差异（P &lt;0.01）。TGH组的脂蛋白胆固醇水平与血浆总甘油三酯（r=0.931，p&lt;0.01）和极低密度脂蛋白胆固醇（r=0.952，p&lt;0.01）呈线性相关。在TGL组中，总胆固醇水平与LDL-胆固醇呈线性相关（r=0.977，p&lt;0.01），但与VLDL-胆固醇无相关性。TGH兔的脂蛋白谱与TGL兔的脂蛋白谱在脂蛋白颗粒大小的变化以及LDL-和VLDL-胆固醇之间的关系方面不同。高脂血症的严重程度由VLDL胆固醇的量确定。因此，本研究建立的高胆固醇血症相关的遗传性高胆固醇血症动物模型将为高胆固醇血症的遗传、代谢和病理生理学研究提供重要的动物模型。

We segregated from WHHL (Watanabe heritable hyperlipidemic) rabbits two strains with high and low levels of hypertriglyceridemia. Selected inbreeding was repeated on the level of plasma triglycerides. Penetrance of a low level (triglyceride<500mg/dl ; TGL group) and a high level (triglyceride>=500mg/dl ; TGH group) of hypertriglyceridemia was 100% and 90% at the 4th generation, respectively. Plasma total cholesterol and triglycerides, measured enzymatically, were 719 <plus-minus> 131 (mean <plus-minus> SD) and 241 <plus-minus> 69mg/dl, respectively in TGL group (9-10 month old rabbits ; n=14) and those in TGH group (other 9-10 month old rabbits ; n=12) were 1239 <plus-minus> 410 (p<0.01 vs TGL group) and 1912 <plus-minus> 1256mg/dl, (p<0.01 vs TGL group), respectively. The lipoproteincholesterol level in the TGH group was linearly related to the total plasma levels of triglyceride (r=0.931, p<0.01) and VLDL-cholesterol (r=0.952, p<0.01). In the TGL group, total cholesterol level was linearly related to LDL-cholesterol (r=0.977, p<0.01), but not to VLDL-cholesterol. Lipoprotein profile of TGH rabbits differed from those of TGL rabbits with regard to the variation of lipoprotein particle size as well as to the relation between LDL-and VLDL-cholesterol. The severity of hypertriglyceridemia was determined by the amount of VLDL cholesterol. Accordingly, the present animal models of heritable hypertriglyceridemia associated with hypercholesterolemia will provide important animal models in genetic, metabolic and pathophysiological analyzes of hyper