载脂蛋白CⅢ转基因小鼠表现明显的高甘油三酯血症  

Severe hypertriglyceridemia appears in apolipoprotein CⅢ transgenic mouse

作　　者：白璐[1] 王宇辉[1] 丁银元[1] 崔鑫[1] 唐寅[1] 黄薇[1] 张玲[1] 刘国庆[1] 

机构地区：[1]北京大学心血管研究所,北京100191

出　　处：《中国病理生理杂志》2010年第11期2235-2239,共5页Chinese Journal of Pathophysiology

摘　　要：目的:建立人载脂蛋白CⅢ(hApoCⅢ)转基因小鼠模型,探讨ApoCⅢ在代谢调节中的作用。方法:应用受精卵显微注射hApoCⅢ基因组片段方法制备转基因小鼠,筛选繁育出稳定遗传的转基因小鼠品系。通过血浆脂质检测、快速蛋白液相色谱脂蛋白分析、口服脂肪负荷试验、肝素后血浆脂蛋白脂酶活性测定以及葡萄糖耐量试验,分析转基因小鼠的脂质和糖代谢特点。结果:成功制备hApoCⅢ转基因小鼠并建立稳定表达的品系,该小鼠表现出显著的高甘油三酯血症[(401±39)mg/dLvs(83±9)mg/dL,P<0.01],并有随年龄增长的趋势。与非转基因小鼠相比,转基因小鼠对甘油三酯(TG)的清除显著延迟,且肝素后血浆脂蛋白脂酶活性也显著降低[(191±42)U/Lvs(368±42)U/L,P<0.05],糖耐量未改变。结论:hApoCⅢ转基因小鼠有明显的高甘油三酯血症,可能与血浆脂蛋白脂酶活性降低所致的血浆TG清除延缓有关。AIM： To investigate the biological functions of human apolipoprotein CⅢ （hApoCⅢ） on metabo-lic regulation, hApoCⅢ transgenic mouse model was established.METHODS： hApoCⅢ transgenic mice were generated by injecting hApoCⅢ genomic fragment into fertilized mouse oocytes, and transgenic line was screened using PCR and Southern blotting. Plasma lipid analysis, fast protein liquid chromatography（FPLC）, oral fat load test, post-heparin plasma lipoprotein lipase（LPL） activity analysis and glucose tolerance test were performed to characterize the phenotypic changes of lipid and glucose metabolism in the transgenic mice.RESULTS： We successfully generated the hApoCⅢ transgenic mouse model, which showed evident hypertriglyceridemia（HTG） , delayed triglyceride（TG） clearance and reduced LPL activity in post-heparin plasma while no change was detected in glucose tolerance test.CONCLUSION： It is suggested that the manifested evident HTG in hApoCⅢ transgenic mice may be due to inhibition of LPL activity in post-heparin plasma, which would lead to a prolonged clearance of plasma TG.

关 键 词：载脂蛋白CⅢ 转基因小鼠 高甘油三酯血症 

分 类 号：R363[医药卫生—病理学]