Kruppel样因子6基因对巨噬细胞中胆固醇蓄积的影响

背景：研究表明,Kruppel样因子6与巨噬细胞极化密切相关。但是,关于Kruppel样因子6在巨噬泡沫细胞形成中的作用尚不清楚。目的：观察Kruppel样因子6过表达对氧化低密度脂蛋白刺激下的小鼠巨噬细胞（RAW264.7）胆固醇蓄积及对ATP结合盒转运蛋白A1表达的影响。方法：取Raw264.7巨噬细胞株分别转染慢病毒空载体和重组载体p CDH-KLF6,作为对照组和Kruppel样因子6组,另取稳定感染慢病毒空载体的Raw264.7巨噬细胞株和稳定感染重组载体p CDH-KLF6的Raw264.7巨噬细胞株均加入50 mg/L氧化低密度脂蛋白共孵育48 h后,得到氧化低密度脂蛋白组和Kruppel样因子6＋氧化低密度脂蛋白组。结果与结论：与对照组相比,氧化低密度脂蛋白组巨噬细胞内总胆固醇和胆固醇酯表达水平显著增加（P〈0.05）。与氧化低密度脂蛋白组巨噬细胞相比,Kruppel样因子6＋氧化低密度脂蛋白组细胞内总胆固醇和胆固醇酯表达水平明显下降,胆固醇酯/总胆固醇明显降低（P〈0.05）。而未加入氧化低密度脂蛋白处理的2组细胞内脂质表达水平少,且对照组与Kruppel样因子6组相比,细胞内脂质表达水平差异无显著性意义。提示Kruppel样因子6可能通过促进ATP结合盒转运蛋白A1的表达,抑制氧化低密度脂蛋白诱导的RAW264.7巨噬细胞胆固醇蓄积。

Effect of Kruppel-like factor 6 overexpression on cholesterol accumulation in macrophages

BACKGROUND： Recent studies have shown that Kruppel-like factor 6 （KLF6） gene is closely related to macrophage polarization. However, the role of KLF6 in the formation of macrophage foam cells is completely unknown. OBJECTIVE： To investigate the effect of KLF6 gene on oxidized low density lipoprotein （ox-LDL）-induced cholesterol accumulation and expression of ATP binding cassette transporter A1 in RAW264.7 macrophages. METHODS： RAW264.7 cell lines were transfected with lentiviral empty vector and recombinant vector carrying pCDH-KLF6, respectively, which acted as control group and KLF6 gene group. RAW264.7 cell lines stably transfected with lentiviral empty vector and recombinant vector carrying pCDH-KLF6 were cultured in 50 mg/L ox-LDL for 48 hours to establish ox-LDL group and ox-LDL＋KLF6 group, respectively. RESULTS AND CONCLUSION： The contents of total cholesterol and cholesterol ester in the ox-LDL group were significantly higher than those in the control group （P 〈 0.05） and the ox-LDL＋KLF6 group （P 〈 0.05）. In addition, the ratio of cholesterol ester to total cholesterol in the ox-LDL group was also lower in the ox-LDL＋KLF6 group than the ox-LDL group （P 〈 0.05）. However, the intrecellular lipid level was lower in the control and KLF6 groups than in the two ox-LDL groups, and there was no difference between the control and KLF6 groups. These findings indicate that KLF6 can upregulate the expression of ATP binding cassette transporter A1 and inhibit the cholesterol accumulation induced by ox-LDL in RAW 264.7 macrophages.