罗格列酮对血管紧张素Ⅱ诱导RAW264.7细胞Toll样受体4表达及髓过氧化物酶活性的抑制作用  

Inhibitory effects of rosiglitazone on angiotensin Ⅱ-induced toll-like receptor 4 expression and myeloperoxidase activity in RAW264.7 cells

作　　者：姬媛媛[1] 王志东[2] 刘俊田[1] 刘娜[1] 

机构地区：[1]西安交通大学医学院药理系,陕西西安710061 [2]西安交通大学第二附属医院普外科,陕西西安710004

出　　处：《南方医科大学学报》2009年第9期1779-1782,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(30772567)

摘　　要：目的探讨罗格列酮对血管紧张素Ⅱ(AngⅡ)诱导的RAW264.7细胞Toll样受体4(TLR4)mRNA和蛋白表达及髓过氧化物酶(MPO)活性的影响及其抗炎、抗动脉粥样硬化机制。方法体外培养RAW264.7细胞。采用RT-PCR检测RAW264.7细胞TLR4mRNA水平,Western blotting检测RAW264.7细胞TLR4蛋白表达,比色法测定细胞培养上清中MPO活性。结果罗格列酮浓度依赖性地下调AngⅡ诱导的RAW264.7细胞TLR4mRNA和蛋白的表达,抑制AngⅡ诱导的RAW264.7细胞MPO活性。此外,TLR4阻断剂对AngⅡ诱导的RAW264.7细胞MPO活性有部分地抑制作用,而罗格列酮可增强这一抑制效应。同时罗格列酮明显地抑制TLR4特异性配体脂多糖的促MPO分泌效应。结论罗格列酮可下调AngⅡ诱导的RAW264.7细胞TLR4表达,并可能通过干预TLR4,影响胞内信号转导途径,抑制MPO分泌,减轻炎症反应,阻止动脉粥样硬化的发生发展。Objective To investigate the effect of rosiglitazone on angiotensin Ⅱ （Ang Ⅲ）-induced rnRNA and protein expressions of toll-like receptor 4 （TLR4） and myeloperoxidase （MPO） activity in RAW264.7 cells to explore its anti- inflammatory and anti-atherosclerotic mechanisms. Methods Murine RAW264.7 cells were pretreated with rosiglitazone at 2.5, 5, and 10 μmol/L prior to exposure to AngⅡ（0.1 μmol/L）. TLR4 mRNA level was analyzed by RT-PCR, and TLR4 protein expression by Western blotting. MPO activity in the cell supernatant was assayed by colorimetry. In another experiment, the cells were pretreated with a neutralizing anti-TLR4 antibody （1 mg/L） for 1 h prior to rosiglitazone （10 μmol/L） treatment for 1 h, and subsequently stimulated with AnglI or LPS （100 μg/L） for 24 h to observe the change of MPO activity. Results Rosiglitazone downregulated AngⅡ-induced mRNA and protein expressions of TLR4, and inhibited MPO activity in RAW264.7 cells in a concentration-dependent manner. The TLR4 blocker partially antagonized the effect of AngⅡ on MPO activity, and the inhibitory effect was markedly enhanced by rosiglitazone. Rosiglitazone significantly inhibited LPS （a specific TLR4 ligand）-induced MPO activity in RAW264.7 cells. Conclusion Rosiglitazone downregulates Ang Ⅱ-induced TLR4 expression in RAW264.7 cells and inhibits MPO secretion possibly by interfering with TLR4 to relieve the inflammatory reaction, which may be one of its anti-atherosclerotic mechanisms.

关 键 词：罗格列酮 血管紧张素Ⅱ TOLL样受体4 髓过氧化物酶 动脉粥样硬化 

分 类 号：R965[医药卫生—药理学]