脂多糖对小鼠巨噬细胞ABCA1表达和胆固醇流出的影响

The Effect of Lipopolysaccharide-Induced Acute Phase Reaction on Expression of ABCA1 in Macrophages of Mice

目的观察脂多糖(LPS)对小鼠腹腔巨噬细胞ATP结合盒转运体A1(ABCA1)表达和胆固醇流出的影响,探讨肝X受体α(LXRα)信号途径的作用。方法 60只C57小鼠分成两组,分别注射LPS(1.0 mg/kg)和等量生理盐水。12 h后取腹腔巨噬细胞,实时荧光定量PCR和Western-blot印迹法检测ABCA1和LXRαmRNA和蛋白质表达水平,液体闪烁计数器检测细胞内胆固醇流出。LXRα激动剂22(R)-羟基胆固醇(22(R)-Hch)预处理小鼠,观察对LPS调节ABCA1表达和胆固醇流出的影响。结果 LPS抑制LXRα和ABCA1的mRNA和蛋白质表达;22(R)-Hch预处理抑制LPS对ABCA1表达和胆固醇流出的下调作用。结论通过抑制TLR4/LXRα信号途径的激活,可以减轻LPS诱导的急性时相反应中的炎症程度,上调ABCA1的表达,促进细胞内胆固醇的流出。

Objective To investigate the effect of lipopolysaccharide（LPS） on the expression of the ABCA1 and cholesterol efflux in macrophages of mice,the role of LXRα in this process was also observed. Methods 60 C57 mice were divided into two groups. The experimental group were treated with LPS （1. 0 mg/kg）. The control group were treated with PBS （1. 0 mg/kg）. After 12 h,the mRNA and protein expression of ABCA1 and LXRα in peritoneal macrophages of mice were examined by reverse transcriptase-polymerase chain reaction（ RT-PCR） and Western-blot. The cholesterol efflux of macrophages was determined by liquid scintillator. The cells were treated with LXRαagonist 22（R）-Hch,and the role of LXRα in the regulated effect of LPS on the expression of ABCA1 were observed. Results LPS decreased the expression of LXRα and ABCA1 in peritoneal macrophages of mice. And the cholesterol efflux of macrophages was also inhibited by LPS. After treated with 22（R）-Hch,the inhibited effect of LPS on expression of ABCA1 and cholesterol efflux were obvious-ly abolished in mice macrophages. LPS-induced acute phase reaction down-regulated the expression of ABCA1 and de-creased cellular cholesterol efflux in macrophages of mice,which may be related to the LXRα-dependent pathway. Con-clusion Inhibiting the activation of signaling pathways TLR4/LXRα,which can reduce inflammation during LPS-induced APR response and increase expression of ABCA1 to promote the outflow of intracellular cholesterol.