高密度脂蛋白对炎症状态下脂肪细胞胆固醇流出的影响

摘要

目的:探讨高密度脂蛋白(High-density lipoprotein,HDL)对体外模拟脂肪细胞炎症状态下胆固醇流出的保护作用及其机制.方法:将前脂肪细胞株3T3-LI(3T3-L1)诱导分化成为成熟的脂肪细胞后,作为空白对照组,脂肪细胞以脂多糖(LPS,100 ng/ml)刺激6小时,为LPS组；脂肪细胞经LPS( 100ng/ml)刺激6小时后,分别用不同浓度HDL孵育16小时,为10 μg/ml HDL+LPS组、50μg/ml HDL+LPS组、100 μg/ml HDL+LPS组.采用液体闪烁计数器检测不同浓度的HDL对LPS刺激的脂肪细胞胆固醇流出的影响,并检测细胞内B族I型清道夫受体(SR-BI)信使核糖核酸(mRNA)和蛋白表达水平.结果:LPS组的胆固醇流出率(2.5±0.6)％较空白对照组(4.1±0.4)％减少,3种不同浓度的HDL+LPS组干预后细胞胆固醇流出率较LPS组增加；LPS组SR-BI mRNA和蛋白表达较空白对照组降低,与LPS组相比较,3种不同浓度的HDL+LPS组SR-BI mRNA和蛋白表达随HDL浓度的增加而递增,差异均有统计学意义(P＜0.05).结论:炎症状态下脂肪细胞的胆固醇流出减少,通过上调SR-BI表达能促进炎性脂肪细胞内胆固醇的流出,减少胆固醇在脂肪细胞内的蓄积.该作用可能与其促进脂肪细胞表达SR-BI有关.%Objective:To investigate the protective role of high-density lipoprotein (HDL) on cholesterol efflux in lipopolysacchride (LPS) stimulated 3T3-L1 adipocytes at inflammatory condition.Methods:3T3-L1 pre-adipocytes were induced to differentiated adipocytes as blank control cells( Control group). Adipocytes were cultured with LPS 100 ng/ml for 6 hours as LPS cells( IPS group). IPS cells were cultured with various concentrations of HDL for 16 hours as LPS cells+10 μg HDL( 10 μg HDL group) ,LPS celk+50 μg HDL(50 μg HDL group) ,and LPS cells+ 100 μg HDL(100 μg HDL group). Cholesterol efflux rate was measured by pre-labeled 3H-cholesterol HDL in conditioned medium. The intracellular( scavenger receptor BI) mRNA and protein expression were examined respectively.Results: The cholesterol efflux rate in LPS group (2. 5 ±0. 6) % was lower than that in Control group (4.1 ±0.4) %. Three HDL+LPS groups had increased cholesterol efflux than that in LPS group,P<0.05 respectively. In LPS group,the SR-BI mRNA and protein expression was lower than those in Control group. Compared with LPS group, the SR-BI mRNA and protein expression were increased with the elevated of HDL concentrations accordingly, P<0.05 respectively. Conclusion:Cholesterol efflux rate decreased in adipocytes at LPS stimulated inflammatory condition. HDL up-regulated SR-BI mRNA and protein expression could promote cholesterol efflux and therefore, reduce the cholesterol accumulation in adipocytes.