脂代谢相关基因在低密度脂蛋白受体基因缺失幼龄小鼠肝脏中的表达分析  

Study on the differential expression of lipid metabolism-related genes in young LDLR knockout mice liver

作　　者：商允菊[1] 戴学栋[1] 荆文[1] 杜会芹[1] 叶红燕[1] 尹苗[1] 张晾[1] 张圣强[1] 李继峰[2] 潘杰[1] 

机构地区：[1]山东师范大学生命科学学院山东省“动物抗性生物学”重点实验室,济南250014 [2]山东师范大学校医院

出　　处：《中华病理学杂志》2008年第3期179-183,共5页Chinese Journal of Pathology

基　　金：国家自然科学基金资助项目（30571024）;山东省教育厅科技计划资助项目（J06L11）

摘　　要：目的探讨脂代谢相关基因在低密度脂蛋白受体（LDLR）基因缺失（LDLR^-/-）小鼠肝脏中的表达特征及其与血脂紊乱和动脉粥样硬化早期病变的关系。方法应用RT-PCR技术分析14、30、60和90天龄LDLR^-/-与野生型（WT）小鼠靶基因表达差异，并进行血生化及主动脉形态学检测。结果与同龄WT小鼠相比，LDLR^-/-小鼠肝脏中载脂蛋白AⅣ、脂肪酸转运酶和肉碱棕榈酰转移酶Ⅰ的mRNA水平在14天龄时即显著下调（P〈0．05）；30天龄时载脂蛋白AⅠ显著上调，载脂蛋白F则显著下调（P〈0．05）；60天龄时肝X受体α显著升高（P〈0．05），酰基辅酶A氧化酶1在90天龄时显著下调（P〈0．05）；载脂蛋白AⅤ、载脂蛋白E、过氧化物增殖物激活受体α和血管生成素样蛋白3差异无统计学意义（P〉0．05）。血清总胆固醇、甘油三酯和低密度脂蛋白C含量从14天龄起均显著高于同龄WT小鼠（均P〈0．05），并随年龄增长持续升高。结论上述脂代谢相关基因在幼龄小鼠即发生表达水平的改变，与血脂紊乱及主动脉病变发生过程呈正相关，说明其可能共同参与幼龄小鼠的脂质代谢紊乱，进而影响动脉内皮细胞功能改变乃至动脉粥样硬化早期病变的发生。Objective To clarify the differential expression of the genes related to the lipid metabolism in the early stage of atherosclerosis in the young LDLR^-/- mice of different ages. Methods A RT-PCR assay was used to analyse the gene expression patterns in the livers of LDLR^-/- mice and wild type （WT） mice from 14 to 90 days. The characteristics of early lipid deposition in intima were evaluated using biochemical and pathological techniques. Results In LDLR^-/- mice, when compared to WT mice, the mRNA level of the apolipoprotein A Ⅳ （ apoA Ⅳ ）, fatty acid translocase （ Fat/CD36 ） and carnitine palmitoyl transferase Ⅰ （CPT Ⅰ ） changed prominently at the age of 14-days （P 〈 0. 05）. At 30 days, the mRNA level of apolipoprotein A Ⅰ （ apoA Ⅰ ） was up regulated, but apolipoprotein F （ apoF）, CD36 and CPT Ⅰ were down regulated （P 〈 0. 05）. At 60 days, the mRNA levels of apoA Ⅰ , CPT Ⅰ and liver X receptor α （LXRα） were up regulated, but apoAiv was down regulated （P 〈0. 05）. At 90 days, the level of the apoA Ⅰ was higher, but the expression of the apoA Ⅳ, apoF and acyl-coenzymeA oxidase 1 （ ACOX1 ） were down regulated （ P 〈 0. 05 ）, whereas the expression of apolipoprotein A Ⅴ （ apoA Ⅴ ）, apolipoprotein E （apoE）, peroxidase proliferator-activated receptor α （PPARα） and angiopoietin-like protein 3 （ angptl 3 ） had no significant changes （ P 〉 0. 05 ）. The serum levels of TC （ P 〈 0. 05 ）, TG （ P 〈 0. 05 ） and LDLC （P 〈 0. 05 ） in LDLR^-/- mice were significantly higher than those in wild type mice with the same age. Conclusions The mRNA levels of the apoA Ⅰ , apoA Ⅳ, apoF, FAT/CD36, CPT Ⅰ , ACOX1 and LXRα of the LDLR^-/- mice were significantly changed compared to the WT mice. The genes may be of some relevance to the complicated lipid metabolism network, and have effect in the early stage of atheregenesis.

关 键 词：受体 LDL 脂代谢障碍 肝脏 动脉粥样硬化 动物实验 

分 类 号：R686[医药卫生—骨科学]