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目的探讨脂联素对巨噬细胞ATP结合盒转运子A1(ATP binding cassette transporter A1,ABCA1)及其上游调控因子肝脏X受体α(Liver X receptorα,LXRα)表达的影响及其在胆固醇逆转运(Reverse cholesterol transport,RCT)和抗动脉粥样硬化(Atherosclerosis,AS)中可能的作用机制。方法以不同浓度的脂联素(0、1、5、10μg/ml)体外培养巨噬细胞RAW264.7 24 h,RT-PCR法检测细胞中ABCA1和LXRα基因mRNA的转录水平,Western blot法检测细胞中ABCA1和LXRα蛋白的表达水平,闪烁计数法检测细胞内胆固醇的流出情况。结果脂联素能显著上调RAW264.7细胞中ABCA1和LXRα基因mRNA的转录水平及蛋白的表达水平(P<0.05),且呈浓度依赖性;脂联素能浓度依赖性地增加细胞内胆固醇的流出(P<0.05)。结论脂联素可通过LXRα途径上调巨噬细胞ABCA1基因的转录和翻译水平,促进胆固醇逆转运,延缓AS的发生、发展。
Objective To investigate the effect of adiponectin on the expression of ATP binding cassette transporter A1 (ABCA1) and its upstream regulatory factor liver X receptor α (LXRα) in macrophages and its effect on cholesterol reverse transport (Reverse cholesterol transport, RCT) and anti-atherosclerosis (Atherosclerosis, AS) possible mechanism of action. Methods Macrophages RAW264.7 cells were cultured in different concentrations of adiponectin (0, 1, 5, 10 μg / ml) for 24 h. The mRNA transcription levels of ABCA1 and LXRα were detected by RT-PCR and Western blot ABCA1 and LXRα protein expression levels in cells, scintillation counting method to detect intracellular cholesterol efflux. Results Adiponectin could up-regulate the mRNA and protein expression of ABCA1 and LXRα in RAW264.7 cells in a concentration-dependent manner (P <0.05). Adiponectin increased the concentration of intracellular cholesterol Outflow (P <0.05). Conclusion Adiponectin can up-regulate the transcription and translation of ABCA1 gene in macrophages through LXRα pathway, promote the reverse cholesterol transport and delay the occurrence and development of AS.