Studies on a model animal for atherogenic lipoproteins and atherosclerosis

目的：研究肝甘油三酯合成增加对致动脉粥样硬化脂蛋白（AS）产生的影响，建立SREBP-1c转基因和LDL受体缺陷双突变小鼠（BP 1c/LDLRKO）模型。BP 1c/LDLRKO显示血浆甘油三酯和胆固醇升高，尤其是在进食时。在琼脂糖电泳上，与LDLR KO小鼠的对照组相比，表明存在残余脂蛋白的broa β条带增加，LIDL胆固醇呈相反降低。肝脏的北方印迹分析显示，过量表达SREBP-1c诱导脂肪生成酶基因如FAS、ACC和SCO的表达。脂肪生成基因表达的激活可以增加肝脏餐后甘油三酯的合成和富含TG的脂蛋白的产生，这些脂蛋白在LDLR转化为血浆中残余脂蛋白的情况下积累。由于这些致动脉粥样硬化脂蛋白的积累，即使在正常饮食下，BP 1c/LDLRKO在8个月龄时也表现出主动脉窦周围的动脉粥样硬化形成。这些小鼠是餐后高脂血症和代谢综合征的良好模型。

To investigate effects of enhanced hepatic trigylcerides synthesis on production of atherogenic lipoproteins, SREBP-lc transgeni and LDL receptor-deficient doubly mutant mice (BP1c/LDLRKO). were generated and their plasma lipoproteins were studied BP1c/LDLRKO showed incrases in plasma triglycerides and cholesterol especially at feeding. On agarose electrophoresis, broa beta band, suggesting presence of remnant lipoproteins was increased and LIDL cholesterol was inversely decreased as compared to controls of LDLR KO mice. Northern blot analysis of livers showed that over-expression of SREBP-lc induced expression of lipogenic enzyme genes such as FAS, ACC, and SCO. Activation of lipogenic gene expression could incrase hepatic postprandia synthesis of triglycerides and production of TG rich lipoproteins, which were accumulated in the absence of LDLR converting to remnant lipoproteins in plasma. Due to the accumulation of these atherogenic lipoproteins, BP1c/LDLRKO exhibited atherorm formation around aortic sinus at age of 8 months even on a regular diet. These mice are a good model for postprandial hyperlipidemia and metabolic syndrome.