白细胞介素1β对美伐他汀处理的HepG2细胞胞内胆固醇含量的影响  

Effects of interleukin 1β on the intracellular cholesterol contents of HepG2 cells treated by compactin

作　　者：周维[1] 王沛[1] 陈压西[1] 阮雄中[1] 赵蕾[1] 

机构地区：[1]重庆医科大学脂糖代谢性疾病重庆市重点实验室,重庆400016

出　　处：《中国临床药理学杂志》2016年第4期343-345,共3页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81200567);高等学校博士学科点专项科研基金资助项目(20105503120004)

摘　　要：目的观察白细胞介素1β(IL-1β)能否干扰美伐他汀降低HepG2细胞内胆固醇含量的作用。方法给予不同浓度的美伐他汀(0,1,10,50,100μmol·L^(-1))单独处理或联合20 ng·mL^(-1)IL-1β处理HepG2细胞24 h。用酶学反应法检测3-羟基3-甲基戊二酸单酰辅酶A还原酶(HMG-CoA-R)的酶活性,用实时荧光定量聚合酶链式反应(Real-Time PCR)方法测定低密度脂蛋白胆固醇(LDL)受体中mRNA的表达水平。然后选取100μmol·L^(-1)美伐他汀单独处理或联合20 ng·mL^(-1)IL-1β处理HepG2细胞24 h,用酶学反应法测定细胞内胆固醇含量,用Real-Time PCR测定细胞内酰基辅酶A-胆固醇酰基转移酶(ACAT)酶表达。结果美伐他汀能显著抑制HepG2细胞的HMG-CoA还原酶活性。IL-1β能有效地削弱美伐他汀对酶活性的抑制作用,同时进一步上调LDL受体的mRNA表达。IL-1β还能促进美伐他汀处理的HepG2细胞中ACAT mRNA的表达,增加细胞内胆固醇酯的含量。结论 IL-1β能增强HepG2细胞的HMG-CoA还原酶活性,促进ACAT酶和LDL受体表达,导致细胞脂质摄入和酯化增加。Objective To investigated the effects of interleukin^（-1）β（ IL-1β） on the intracellular cholesterol contents of HepG2 cells treated by compactin. Methods HepG2 cells were treated with different concentrations of compactin（ 0,1,10,50,100 μmol·L^（-1）） in the absence or presence of 20 ng·mL^（-1）IL-1β for 24 hours. Commercial kits was used to evaluated the enzymatic activity of 3- hydroxy- 3- methyl- glutaryl（ HMG）- Co A reductase（ HMG- Co A- R）. Real- time PCR was used to determine the mRNA of low density lipoprotein（ LDL） receputer. Then HepG2 cells treated with 100 μmol · L^（-1）compactin in the absence or presence of 20 ng·mL^（-1）IL-1β were chose to evaluated the content of intracellular cholesterol by commercial kits,real- time PCR was used to determine the mRNA of acyl coenzyme A- cholesterol acyltransferase（ ACAT）. Results Compactin dose dependently reduced HMG- Co A- R enzymatic activity. IL-1β upregulated the enymatic activity of HMG- Co A reductase,LDL receptor,and the expression of acyl- coenzyme A- cholesterol acyltransferase mRNA, which was accompanied with increased intracellular cholesterol ester contents.Conclusion Inflammatory cytokine disrupted the suppressive effect of compactin on the HMG- Co A- R enzymatic activity in HepG2 cells and increased the expression of ACAT and LDL receptor and may contribute to hepatic cholesterol accumulation under inflammatory conditions.

关 键 词：美伐他汀 白细胞介素1Β 胆固醇 HEPG2细胞 

分 类 号：R972.6[医药卫生—药品] R968[医药卫生—药学]