辛伐他汀对氧化型低密度脂蛋白及葡萄糖诱导的LOX-1表达的不同作用

【摘要】目的研究辛伐他汀干预对于氧化型低密度脂蛋白（ox-LDL）及葡萄糖诱导的巨噬细胞表面血清凝集素样氧化型低密度脂蛋白受体（LOX）-1表达的影响，以及核因子（NF）-κB的作用。方法U937细胞经佛波酯诱导分化后，将含有50mg/L ox-LDL和（或）25mmol/L葡萄糖的培养液与上述细胞共同孵育，应用吡咯烷二硫氨基甲酸（PDTC）及不同浓度辛伐他汀（1、10μmol/L）干预上述细胞，干预前后用ELISA检测LOX-1蛋白的表达及NF-κB的活性，RT-PCR检测LOX-1mRNA含量。结果ox-LDL、高糖及联合组均上调LOX-1表达，NF-κB的抑制剂PDTC可以抑制其作用，辛伐他汀可以下调ox-LDL诱导的LOX-1表达增加，且高浓度下调明显；但辛伐他汀对于高糖诱导LOX-1表达无明显影响。各组间NF-κB活性改变与LOX-1表达基本一致。结论辛伐他汀可以下调ox-LDL诱导的巨噬细胞LOX-1表达，但对葡萄糖诱导的LOX-1表达无明显影响，LOX-1表达调控与NF-κB信号途径有关。

Different Effects of Simvastatin on the Expression of Lectin-like Oxidized Low-Density Lipoprotein Receptor-1(LOX-1) Induced by Oxidized Low-Density Lipoprotein(ox-LDL) or Glucose

Abstract]ObjectiveTo investigate the effects of simvastatin on the expression of lectin-like oxidized low-densitylipoprotein receptor-1(LOX-1) induced by oxidized low-density lipoprotein (ox-LDL) or Glucosein U937 macrophages ,and explore the role of NF-κB in modulating of LOX-1expression.MethodsU937macrophages were treated with PMA toinduce differentiation, which were co-cultured with 50mg/L ox-LDL or/and25mmol/L glucose. Pyrrolidine dithiocarbamate(PDTC) and simvastatin (1μmol/L or10μmol/L) were used to treat cells. The expression of LOX-1protein and NF-κB activity were detected by enzyme-linked immunosorbent assay technology. The expression of LOX-1mRNA was measured by RT-PCR.ResultsThe expression of LOX-1was up regulated by ox-LDL, glucose and combination of both. The inhibitor of NF-κB PDTC suppressed this up-regulation. Simvastatin suppressed the expression of LOX-1induced by ox-LDL, and showed a significant effect in the higher concentration. There was no significant effect of simvastatin on the expression of LOX-1induced by glucose. The variation of NF-κB activity was similar to that of LOX-1expression.ConclusionSimvastatin suppressed the expression of LOX-1induced by ox-LDL, while no significant effect on the expression of LOX-1induced by glucose. The expression and regulation of LOX-1were related with NF-κB pathway.