芳香烃受体和雄激素受体对HepG2细胞中脂质代谢影响的研究

Effects of Aryl Hydrocarbon Receptor and Androgen Receptor on Lipid Metabolism in HepG2 Cells

关键词:  芳香烃受体  雄激素受体  脂质代谢  6-甲酰基吲哚并[3,2-B]咔唑  二氢睾酮

Key words:  aryl hydrocarbon receptor  androgen receptor  lipid metabolism  6-Formylindolo[3,2-b]carbazole  dihydrotestosterone

摘要:

摘要：目的 探究芳香烃受体(Aryl hydrocarbon receptor，AhR)和雄激素受体(Androgen receptor，AR)对HepG2细胞中脂质代谢的影响。方法 将HepG2细胞分为Control组、6-甲酰基吲哚并[3,2-B]咔唑(6-Formylindolo[3,2-b]carbazole,FICZ) (AhR激动剂)组、二氢睾酮(Dihydrotestosterone, DHT) (AR激动剂)组、FICZ+DHT组，按分组分别给予HepG2细胞1 μmol·L-1 FICZ及1 μmol·L-1DHT。试剂盒检测TG、TC和 LDL-C含量，油红O染色法检测脂质含量，尼罗红染色法检测脂质荧光强度。Western blot法检测胆固醇合成相关基因3-羟基-3-甲基戊二酸还原酶(3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase，HMGCR)、固醇调节元件结合蛋白2(Sterol regulatory element-binding protein 2，SREBP2)、肝X受体α(Liver X Receptor alpha，LXRα)和脂肪酸合成的相关基因CCAAT增强子结合蛋白α(CCAAT Enhancer Binding Protein alpha，C/EBPα)、过氧化物酶体增殖物激活受体γ(Peroxisome proliferator-activated receptor?γ，PPARγ)和硬脂酰辅酶A去饱和酶1(Stearoyl-CoA Desaturase 1，SCD1)蛋白的表达情况。结果 与Control组相比，FICZ组HepG2细胞中脂质含量上升，DHT组HepG2细胞中脂质含量降低；与FICZ组相比，FICZ+DHT组HepG2细胞中脂质含量降低。与Control组相比，FICZ组HMGCR、SREBP2、LXR蛋白表达增加；DHT组HMGCR、SREBP2、LXRα蛋白表达减少；与FICZ组相比，FICZ+DHT组HMGCR、SREBP2、LXRα蛋白表达减少。与Control组相比，FICZ组SCD1、C/EBPα、PPARγ蛋白表达增加；DHT组SCD1、C/EBPα、PPARγ蛋白表达减少；与FICZ组相比，FICZ+DHT组SCD1、C/EBPα、PPARγ蛋白表达减少，差异具有统计学意义。结论 AhR和AR存在相互作用，对脂质代谢的影响呈相互拮抗。

Abstract:

ABSTRACT: OBJECTIVE To investigate the effects of aryl hydrocarbon receptor (AhR) and androgen receptor (AR) on lipid metabolism in HepG2 cells. METHODS HepG2 cells were divided into Control group, 6-Formylindolo[3,2-b]carbazole (FICZ) (AhR agonist) group,Dihydrotestosterone (DHT) (AR agonist) group, and FICZ+DHT group. HepG2 cells were given 1 μmol·L-1 FICZ and 1 μmol·L-1 DHT according to the groups. Kits were used to detect the levels of TG, TC and LDL-C, Oil Red O staining was used to detect lipid content, and Nile Red staining was used to detect lipid fluorescence intensity. Western blot was used to detect the expression of cholesterol synthesis-related genes 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGCR), Sterol regulatory element-binding protein 2 (SREBP2), Liver X Receptor alpha (LXRα) and fatty acid synthesis-related genes CCAAT Enhancer Binding Protein alpha (C/EBPα), Peroxisome proliferator-activated receptor?γ (PPARγ) and Stearoyl-CoA Desaturase 1 (SCD1) proteins. RESULTS Compared with the Control group, the lipid content in HepG2 cells in the FICZ group increased, and the lipid content in HepG2 cells in the DHT group decreased; compared with the FICZ group, the lipid content in HepG2 cells in the FICZ+DHT group decreased. Compared with the Control group, the expression of HMGCR, SREBP2, and LXRα proteins in the FICZ group increased; the expression of HMGCR, SREBP2, and LXRα proteins in the DHT group decreased; compared with the FICZ group, the expression of HMGCR, SREBP2, and LXRα proteins in the FICZ+DHT group decreased. Compared with the Control group, the expression of SCD1, C/EBPα, and PPARγ proteins in the FICZ group increased; the expression of SCD1, C/EBPα, and PPARγ proteins in the DHT group decreased; compared with the FICZ group, the expression of SCD1, C/EBPα, and PPARγ proteins in the FICZ+DHT group decreased, and the differences were statistically significant. CONCLUSION AhR and AR interact with each other and their effects on lipid metabolism are antagonistic.