DHA缓解肝X受体激活所致HepG2细胞的甘油三酯积聚

目的探讨DHA对肝X受体激动剂T0901317诱导的HepG2细胞甘油三酯积聚的影响。方法体外培养HepG2细胞，以50μmol／LDHA、10μmol／LT0901317分别处理细胞以及50μmloL／LDHA和10μmol／LT0901317共同处理细胞48h。油红0染色观察细胞内脂质沉积；氯仿-甲醇抽提细胞总脂质，酶法定量检测细胞甘油三酯含量；实时定量PCR检测与脂肪酸代谢相关基因如SREBP-1c、FAS、SCD-1、PPARa和CD36的mRNA水平。结果与对照组相比，10μmol／LT0901317处理48h后，HepG2细胞内的油红O染色脂滴增多，甘油二酯浓度升高了50％；脂肪酸合成基因：SREBP-1c、FAS和SCD-1及脂肪酸吸收基因CD36的mRNA水平分别升高了9．9、5．2、2．2和1．5倍，而脂肪酸降解基因PPARoz的mRNA无变化。DHA与T0901317共同处理的HepG2细胞内脂滴明显减少；甘油三酯含量比70901317处理组降低了15％：SREBP—1c、FAS、SCD-1和CD36的mRNA水平比T0901317处理组分别降低了92％、31％、46％和60％，而PPARa的mRNA水平比T0901317处理组升高了30％。结论DHA通过降低脂肪酸合成和吸收基因的表达并升高脂肪酸降解基因的表达缓解肝x受体激活所致HepG2细胞内甘油三酯积聚。

DHA Attenuates LXR Activation-induced Triglyceride Accumulation in HepG2 Cells

Objective The aim of this study was to determine the role of DHA in LXR activation-induced triglyceride accumulation in HepG2 cells. Methods HepG2 cells were treated with 50μmol/L DHA, 10 μmol/L T0901317 （LXR agonist） or combination of 10 txmol/L T0901317 and 50 μmol/L DHA for 48 h. The lipid droplets in HepG2 were observed by oil red O staining. The cellular lipids were extracted and contents of triglyceride were measured by enzymatic methods. The mRNA levels of genes that are involved in lipogeuesis （SREBP-lc, FAS and SCD-1 ） , fatty acid degradation （PPARα） and fatty acids absorption （CD36） were analyzed by real-time quantitative PCR. Results Compared with untreated l-IepG2 ceils, the size and number of lipid droplets were largely increased in T0901317-treated HepG2 cells. T0901317 treatment increased the contents of cellular triglyceride by 50 % , accompanied with enhanced mRNA levels of SREBP-lc, FAS, SCD- 1 and CD36, but not PPARcx. However, combination treatment of I4epG2 ceils with T0901317 and DHA decreased the size and number of lipid droplets, the cellular triglyceride contents and mRNA levels of SREBP-1c, FAS, SCD-1 and CD36, but increased mRNA levels of PPARα. Conclusion DI-tA attenuates LXR activator T0901317-induced triglyceride accumulation by down-regulating the genes involved in lipogenesis and fatty acid absorption and up-regulating the genes involved in fatty acid degradation.