非诺贝特通过上调PPARα抑制LPS诱导的THP-1细胞TLR4表达的实验研究  

Fenofibrate suppresses LPS-induced TLR4 expression through up-regulation of PPARαin THP-1 cells

作　　者：王卫远[1] 李俊芳[1] 聂尚燕[2] 刘曦[1] 赵阳[1] 

机构地区：[1]邯郸市中心医院免疫科,河北邯郸056001 [2]邯郸市中心医院感染科,河北邯郸056001

出　　处：《西部医学》2016年第1期32-35,共4页Medical Journal of West China

摘　　要：目的探讨PPARα激动剂非诺贝特对LPS诱导的人单核细胞系THP-1细胞TLR4表达的调控作用,以及潜在的分子机制。方法将THP-1细胞分为4组即对照组(Control组)、LPS组、LPS+非诺贝特(LPS+Feno组)和LPS+非诺贝特+PPARα拮抗剂GW6471组(LPS+Feno+GW组)。在干预4小时后使用qPCR法和western blotting法对THP-1细胞TLR4和PPARαmRNA和蛋白的表达水平进行检测。结果与Control组相比较,在LPS干预4小时后THP-1细胞TLR4mRNA和蛋白的表达水平明显增加,PPARαmRNA和蛋白的表达水平明显下降,差异均有显著统计学意义(P均<0.05);但LPS组较LPS+Feno组TLR4表达的增加水平和PPARα表达的下降水平更加明显,差异均有显著统计学意义(P均<0.05)。同时,在LPS刺激状态下非诺贝特对于TLR4和PPARαmRNA和蛋白的表达的改善作用可被PPARα拮抗剂GW6471显著抑制,差异均有显著统计学意义(P均<0.05)。结论在LPS诱导的炎症状态下,非诺贝特可以通过上调PPARα的转录合成抑制THP-1细胞TLR4表达,最终减轻炎症水平。研究表明非诺贝特具有潜在的炎症调控作用,为非诺贝特等PPARα激动剂应用于炎症性疾病的临床治疗奠定了一定的理论基础。Objective To explore the value of fenofibrate in LPS-enhanced TLR4 expression in THP-1 cells and its underlying molecular mechanism. Methods THP-1 cells were divided into ate＋PPARα inhibitor GW6471 group （LPS-t- Feno＋GW group）. After 4 hours interventions, qPCR and western blotting were used to measure the mRNA and protein expression of TLR4 and PPARa in THP-1 cells. Results After 4 hours LPS stimulation, the mRNA and protein expres- sion of TLR4 was remarkably enhanced, and the mRNA and protein expression of PPARa was significantly reduced. Then, we found that LPS-enhanced expression of TLR4 and LPS-reduced PPARα were noticeably improved by fenofi- brate in THP-1 cells. Furthermore, our data also figured out that these effects of fenofibrate were substantially blocked by PPARa inhibitor GW6471. Conclusion Fenofibrate inhibited LPS-enhanced TLR4 expression probably via up-regula tion of PPARa in THP 1 cells.

关 键 词：非诺贝特 THP-1细胞 TOLL样受体4 氧化物酶体增殖激活受体α GW6471 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]