激动β_3肾上腺素能受体上调载脂蛋白A-Ⅰ促进泡沫细胞胆固醇流出的研究  

β_3-adrenoceptor activation promotes cholesterol efflux from foam cells by upregulating apoA-Ⅰexpression

作　　者：高夏青[1] 李艳芳[1] 

机构地区：[1]首都医科大学附属北京安贞医院急诊综合病房,100029

出　　处：《中华老年心脑血管病杂志》2017年第1期20-24,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

摘　　要：目的通过激动或抑制HepG2细胞的β3肾上腺素能受体(β3-AR),探讨β3-AR调节胆固醇逆转运过程的可能机制。方法将培养的HepG2细胞随机分为对照组、β3-AR激动剂组(激动剂组)和β3-AR拮抗剂组(拮抗剂组),ELISA法检测上清液载脂蛋白(apo)A-Ⅰ、apoA-Ⅱ及β3-AR水平;测定细胞内胆固醇、游离胆固醇和胆固醇酯水平,3 H标记的胆固醇测定胆固醇流出率,实时定量PCR和蛋白印迹法分别检测细胞中三磷酸腺苷结合盒转运蛋白A1(ABCA1)和肝X受体α亚型(LXRα)的表达。结果与对照组比较,激动剂组apoA-Ⅰ、游离胆固醇、胆固醇流出率显著增加,胆固醇、胆固醇酯显著降低,ABCA1和LXRαmRNA及ABCA1和LXRα蛋白显著增加;拮抗剂组胆固醇、胆固醇酯显著升高,apoA-Ⅰ、胆固醇流出率显著减少,ABCA1和LXRαmRNA及ABCA1和LXRα蛋白显著降低。与激动剂组比较,拮抗剂组ABCA1和LXRαmRNA及ABCA1和LXRα蛋白显著降低(0.49±0.10 vs1.24±0.02,0.85±0.05 vs 1.32±0.05,0.38±0.01 vs 1.45±0.20,0.08±0.01 vs 0.76±0.02,P<0.01)。结论激动HepG2细胞的β3-AR,可上调apoA-Ⅰ表达,促进巨噬细胞源性泡沫细胞胆固醇逆转运相关蛋白的表达。Objective To study the mechanism ofβ3adrenoceptor（β3-AR）activation underlying cholesterol efflux by activating or inhibiting theβ3-AR of HepG2 cells.Methods Cultured HepG2 cells were randomly divided into control group,β3-AR agonist group andβ3-AR antagonist group.Serum levels of apoA-Ⅰ,apoA-Ⅱ,andβ3-AR in supernatant fluid,and cholesterol,free cholesterol,cholesterol ester in HepG2 cells were measured by ELISA.Cholesterol efflux from macrophages was tested by 3 H-labled cholesterol.Expressions of ABCA1 and LXRα mRNA and protein were detected by RT-PCR and Western blot respectively.Results The efflux rate of apoA-Ⅰ,cholesterol and cholesterol ester was significantly higher while the serum levels of cholesterol and cholesterol ester were significantly lower and the expression levels of ABCA1 and LXRαmRNA and protein were significantly higher inβ3-AR agonist group than in control group.The serum levels of cholesterol and cholesterol ester were significantly higher while the efflux rate of cholesterol and cholesterol ester and the expression levels of ABCA1 and LXRαmRNA and protein were significantly lower inβ3-AR antagonist groupt than inβ3-AR agonist group（0.49±0.10 vs 1.24±0.02,0.85±0.05 vs 1.32±0.05,0.38±0.01 vs 1.45±0.20,0.08±0.01 vs 0.76±0.02,P〈0.01）.Conclusion β3-AR promotes cholesterol efflux by upregulating the expression of apoA-Ⅰin HepG2 cells.

关 键 词：受体 肾上腺素能β3 载脂蛋白A-Ⅰ 泡沫细胞 胆固醇 

分 类 号：R543.5[医药卫生—心血管疾病]