高脂高胆固醇饮食对apoE-/-/LDLR-/-/Leprdb/db小鼠肝组织基因表达差异的影响

目的：研究高脂高胆固醇饮食对三基因突变(apoE-/-/LDLR-/-/Leprdb/db)小鼠肝脏基因表达的影响, 分析这些差异表达基因与血脂代谢紊乱和动脉粥样硬化（AS）的关系。 方法： 利用cDNA表达谱芯片检测普通饮食和高脂高胆固醇饮食喂养的三基因突变小鼠肝脏基因表达差异;分别用COD-PAP,GPO-PAP法测定血浆总胆固醇（TC）和甘油三酯（TG）浓度;并观察了主动脉形态变化。 结果： 在被测的4 000条基因中，高脂高胆固醇饮食组较普通饮食组小鼠上调基因为78条，下调114条，包括脂代谢、糖代谢、细胞骨架蛋白和免疫与炎症等相关基因。高脂高胆固醇饮食组血浆TC和TG水平均高出普通饮食组。5周龄时，两组小鼠均有主动脉内膜损伤，而高脂高胆固醇饮食组重于普通饮食组，并随年龄增长而加重。 结论： 高脂高胆固醇饮食对三基因突变小鼠血脂代谢紊乱乃至AS的发生发展有明显促进作用。

Effects of high fat/high cholesterol diet on differentially expressed gene of the liver in treble genes mutant mice

AIM: To study the effects of dietary factor on liver gene expression profile in apoE~(-/-)/LDLR~(-/-)/Lepr~(db/db) mice and atherogenesis. METHODS: The gene expression profile was determined by using cDNA microarray. Total plasma TC and TG level were measured with COD-PAP and GPO-PAP methods respectively. The morphological characters of the aorta were also observed. RESULTS: Among the 4000 target genes, 78 and 114 genes were up-and down-regulated, respectively, in treble genes mutants fed with high fat high cholesterol diet compared with that of regular chow littermates, including lipid metabolism, carbohydrate, cell skeleton and immune related genes. Atherogenic diet induced severe plasma hyperlipidemia even in the early stage and also accelerated atherogenesis in the treble genes mutant mice. CONCLUSION: The data suggest that atherogenic diet aggravates abnormal plasma lipid metabolism and induces severe hyperlipidemia, and atherogenesis in the treble genes mutant mice as well.