高糖刺激对人THP-1巨噬细胞肝X受体和三磷酸腺苷结合盒转运子A1表达的作用

目的 探讨高糖对人THP-1巨噬细胞肝X受体（LXR）和三磷酸腺苷结合盒转运子A1（ABCA1）表达的影响。 方法 人THP-1单核细胞经佛波脂（PMA）诱导转化成巨噬细胞。用CD68检测巨噬细胞表面标志物表达。以不同浓度葡萄糖（5.6、11.1、22.2、33.3 mmol/L）和不同时间（0、0.5、2、6、12、24、48、72 h）刺激巨噬细胞，用实时荧光定量PCR法检测其LXRα、LXRβ、ABCA1 mRNA表达；Western 印迹法检测LXRα、LXRβ和ABCA1蛋白的表达，并分析其相互间作用。 结果 PMA诱导72 h后，TPH-1细胞CD68呈阳性表达。与正常浓度糖（5.6 mmol/L）刺激比较，高糖刺激24 h后，TPH-1巨噬细胞LXR和ABCA1 mRNA和蛋白表达均下调。高糖刺激30 min后， LXRα、LXRβ和ABCA1 mRNA和蛋白表达上调；2 h后开始下调，随着时间延长而逐渐减少。 结论 高糖可能通过抑制LXR和ABCA1的表达，参与了动脉粥样硬化的发生和发展。

Effect of high glucose on the expression of liver X receptors and ABCA1 in human THP-1 macrophages

Objective To investigate the effect of high glucose on the expression of liver X receptors (LXRs) and ATP-binding cassette transporter A1 (ABCA1) in human macrophages (THP-1 cell line). Methods THP-1 monocytes were differentiated into macrophages by induction of phorbol 12, 13-dibutyrate (PMA). Surface markers of macrophages were identified by CD68 immunohistochemistry. The macrophages were cultured with different concentration (5.6, 11.1, 22.2 and 33.3 mmol/L) of glucose and different time (0, 0.5, 2, 6, 12, 24, 48, 72 h). Real time PCR and Western blotting methods were used to examine the mRNA and protein expression of LXRs and ABCA1. Results As compared to 5.6 mmol/L glucose, macrophage LXRβ and ABCA1 were decreased significantly at both mRNA and protein levels in dose-and time-dependent manner (P<0.05). Conclusion Hyperglycemia may play a role in the pathogenesis of arteriosclerosis through the inhibition of LXRs and ABCA1 expression in diabetic patients.