阿托伐他汀对HepG2细胞中脂代谢相关基因表达的影响

摘要

Objective:To explore the effects of atorvastatin on the natural antisense transcription of apolipoprotein A1 (apoA1-NAT) in the HepG2cells and its influence in the expressions of lipid metabolism related genes.Methods:The HepG2cells were intervened with different concentrations (0, 1, 10and 100nmol·L-1) of atorvastatin, and the 0nmol·L-1 atorvastatin group was used as control group.The total RNA of HepG2cells in various groups were extracted at different time points (6, 12, 24, and 48h) .The mRNA expression levels of lipid metabolism-related genes and apoA1-NAT expression levels were detected by Real-Time PCR method.Results:The morphology of HepG2 cells in 1and 10nmol·L-1 atorvastain groups was normal.Compared with 6h, the expression levels of apoA1-NAT in the HepG2cells in 10nmol·L-1 atorvastatin group at 12, 24and 48hwere significantly decreased (P＜0.01) in a time-dependent manner.Under the same condition, the expression level of apoA1mRNA in the HepG2cells at 48hwas increased significantly compared with 6h (P＜0.01) .Compared with control group, the expression levels of low density lipoprotein receptor (LDLR) in the HepG2 cells in100nmol·L-1 atorvastatin group, scavenger receptor-class B type 1 (SRB1) in 10nmol·L-1 atorvastatin group and ATP binding cassette transporter A1 (ABCA1) in 1and 10nmol·L-1 atorvastatin groups were increased (P＜0.01) in different degrees.Conclusion:Atorvastatin can promote the expressions of lipid metabolism-related genes by inhibiting the expression of apoA1-NAT, and promote the process of reverse cholesterol transport.%目的:探讨阿托伐他汀对HepG2细胞中载脂蛋白A1 (apoA1) 天然反义转录 (apoA1-NAT) 的作用及对脂代谢相关基因表达的影响.方法:采用不同浓度阿托伐他汀 (0、1、10和100nmol·L-1) 干预HepG2细胞, 0nmol·L-1阿托伐他汀组为对照组, 在不同时间点 (6、12、24和48h) 提取各组HepG2细胞总RNA, 采用Real-time PCR法检测HepG2细胞中apoA1-NAT和脂代谢相关基因mRNA表达水平.结果:1和10nmol·L-1阿托伐他汀组HepG2细胞形态正常.与6h时比较, 12、24和48h时10nmol·L-1阿托伐他汀组HepG2细胞中apoA1-NAT表达水平明显降低 (P＜0.01) , 且呈明显的时间依赖性.在相同条件下, 48h时HepG2细胞中apoA1mRNA表达水平较6h时明显升高 (P＜0.01) .与对照组比较, 100nmol·L-1阿托代他汀组HepG2细胞中低密度脂蛋白受体 (LDLR) 、10nmol·L-1阿托代他汀组HepG2细胞中清道夫受体B1 (SRB1) 及1和10nmol·L-1阿托伐他汀组HepG2细胞中ATP结合盒式转运体A1 (ABCA1) 表达水平均有不同程度升高 (P＜0.01) .结论:阿托伐他汀通过抑制HepG2细胞中apoA1-NAT表达, 促进脂代谢相关基因表达, 进而促进胆固醇逆转运过程.