【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。更多还原

【Abstract】 Objective To explore the value of fenofibrate in LPS-enhanced TLR4 expression in THP-1cells and its underlying molecular mechanism.Methods THP-1cells were divided into ate+PPARαinhibitor GW6471group(LPS+Feno+GW group).After 4hours interventions,qPCR and western blotting were used to measure the mRNA and protein expression of TLR4 and PPARαin THP-1cells.Results After 4hours LPS stimulation,the mRNA and protein expression of TLR4 was remarkably enhanced,and the mRNA and protein expression of PPARαwas significantly reduced.Then,we found that LPS-enhanced expression of TLR4 and LPS-reduced PPARαwere noticeably improved by fenofibrate in THP-1cells.Furthermore,our data also figured out that these effects of fenofibrate were substantially blocked by PPARαinhibitor GW6471.Conclusion Fenofibrate inhibited LPS-enhanced TLR4 expression probably via up-regulation of PPARαin THP-1cells.更多还原