非诺贝特对血管紧张素II诱导RAW264.7细胞Toll样受体4表达, 髓过氧化物酶活性及表达的抑制作用

探讨非诺贝特对血管紧张素Ⅱ (AngⅡ) 诱导的小鼠巨噬细胞株RAW264.7细胞Toll样受体4 (TLR4) mRNA、蛋白表达及髓过氧化物酶 (MPO) 活性、mRNA及蛋白表达的影响及其抗炎机制。采用RT-PCR检测TLR4和MPO mRNA水平, Western blotting检测TLR4和MPO的蛋白表达，比色法测定细胞培养上清液中的MPO活性。结果显示，非诺贝特浓度依赖性地减少AngⅡ诱导的RAW264.7细胞TLR4 mRNA及蛋白表达，抑制AngⅡ诱导的RAW264.7细胞MPO活性、mRNA及蛋白表达。此外，TLR4阻断剂对AngⅡ诱导的RAW264.7细胞MPO活性有部分的抑制作用，而非诺贝特可增强这一抑制效应。同时非诺贝特明显拮抗TLR4特异性配体脂多糖的促MPO分泌效应。以上结果表明，非诺贝特可下调AngⅡ诱导的RAW264. 7细胞TLR4表达，并通过干预TLR4，影响胞内信号转导途径，抑制MPO分泌，减轻炎症反应，这可能是其新的抗炎机制之一。

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

This study is to investigate the effect of fenofibrate on angiotensin II (Ang II)-induced toll-like receptor 4 (TLR4) expression, myeloperoxidase (MPO) activity and expression in murine macrophage line RAW264.7 cells and explore its anti-inflammatory mechanism.  TLR4 and MPO mRNA levels were analyzed by RT-PCR, and TLR4 and MPO protein expressions were measured by Western blotting.  MPO activity in the cell supernatant was assayed with colorimetry.  The results showed that fenofibrate reduced AngⅡ-induced mRNA and protein expression of TLR4 and inhibited activity, mRNA and protein expression of MPO in RAW264.7 cells in concentration-dependent manner.  In addition, TLR4 blocker partially antagonized the effect of AngⅡ on MPO activity in RAW264.7 cells, and fenofibrate potentiated the inhibitory effect.  Meanwhile, fenofibrate significantly suppressed LPS (TLR4 special ligand)-induced MPO activity in RAW264.7 cells.  In conclusion, fenofibrate downregulated AngⅡ-induced TLR4 expression and blocked MPO secretion in RAW264.7 cells via interfering with the TLR4-dependent signaling pathway to alleviate inflammation, which might be one of its novel anti-inflammatory mechanisms.