【摘要】 目的研究3个脂代谢相关基因联合突变小鼠与野生型小鼠肝脏基因表达差异及其与血脂代谢紊乱和动脉粥样硬化病变的关系。方法应用BiostarM-40S型小鼠cDNA表达谱芯片检测不同基因型小鼠肝脏基因表达的差异,并观察不同年龄小鼠血浆总胆固醇和甘油三脂的浓度以及主动脉内膜形态变化。结果在被测的4000条基因中,与野生型小鼠比较,5周龄三基因突变小鼠肝脏基因表达上调92条,下调105条,脂代谢相关基因中与胆固醇合成相关的基因表达下调,与甘油三脂代谢相关的肝脂肪酶基因表达水平上调。糖代谢、细胞骨架蛋白和免疫等相关的基因表达也有明显差异。5周龄的三基因突变小鼠血浆总胆固醇和甘油三脂水平明显高于野生型小鼠,伴有主动脉内膜损伤,并随年龄增长而加重。结论三基因突变导致肝脏中与脂类、糖类以及免疫等相关的多种基因表达改变,可能共同参与了血脂代谢紊乱和动脉粥样硬化的发生发展。更多还原

【Abstract】 Objective To study the gene expression profile of liver of young apoE~-/- /LDLR~-/- /Lepr~db/db treble genes mutant mice and disclose its relationship to hyperlipidemia and the following atherosclerotic lesion. Methods The gene expression profile was investigated using cDNA microarray technique; the plasma total cholesterol(TC) and triglyceride(TG) levels were analyzed by COD-PAP and GPO-PAP method. And morphological observations of the aorta were made. Results Among the 4000 target genes, 92 genes were up-regulated and 105 genes were down-regulated in the treble genes mutants, compared with wild type control. Among the differentially expressed lipid metabolism related genes, cholesterol synthesis gene coding for farnesyl diphosphate farnesyl transferase was down-regulated, while triglyceride metabolism gene e.g. pancreatic lipase related protein 1 gene (Pnliprp1) was up-regulated. Expression profile of carbohydrate, cell skeleton and immune related genes were also altered. On the other hand, in the plasma from the treble genes mutant mice at 5 weeks of age, hyperlipidemia was found to be combined with atheroslerotic lesion. All these biochemical and pathological changes were aggravated following aging. Conclusion The data suggested that the multiple genes mutations, especially those involved in lipid metabolism, were contributing to the alteration of liver gene expression profile that might lead to hyperlipidemia and atherosclerotic lesion in the young apoE~-/- /LDLR~-/- /Lepr~db/db mutants.更多还原