中文摘要：

目的探讨氟伐他汀对脂多糖（LPS）刺激的人急性单核细胞白血病细胞系（THP-1）Toll样受体4（TLR4）及下游信号转导通路的干预作用。方法采用不同剂量的氟伐他汀、LPS处理THP-1细胞,MTT法检测细胞增殖情况,实时荧光定量RTPCR（qRT-qPCR）检测细胞中TLR4和肿瘤坏死因子-α（TNF-α）mRNA的表达,western blot检测TLR4及下游磷酸化胞外信号调节激酶（ERK）、磷酸化核因子κB（NF-κB p65）蛋白的表达水平。ELISA法测定细胞培养上清中TNF-α蛋白的含量。结果氟伐他汀（10 mg/L）降低LPS刺激的THP-1细胞TLR4（蛋白质和mRNA）的表达（t分别为7.55、7.80,P均〈0.05）,1、5、10mg/L氟伐他汀能显著抑制LPS刺激的下游分子ERK的磷酸化（q分别为11.78、18.15、18.88,P〈0.05）;亦能抑制LPS刺激的NF-κB p65的磷酸化（q分别为5.13、6.87、11.68,P〈0.05）。同时,氟伐他汀（10 mg/L）能显著干预LPS刺激的细胞TNF-α（蛋白质和mRNA）的表达（q分别为4.23、3.01,P〈0.05）。结论氟伐他汀可通过干预LPS刺激的TLR4表达及下游分子ERK、NF-κB p65的磷酸化,抑制THP-1细胞TNF-α的表达,可能为氟伐他汀的抗炎机制之一。

英文摘要：

Objective To investigate the interference effect of fluvastatin on the expression of Toll-like receptor 4（ TLR4） and its downstream signal transduction pathway in THP-1 cells,an acute monocytic leukemia cell line. Methods After THP-1 cells were treated with lipopolysaccharide（LPS） and different concentrations of fluvastatin,the proliferation ability of THP-1 cells was detected by MTT assay,the mRNA levels of TLR4 and tumor necrosis factor-α（TNF-α） in THP-1 cells by real time quantitative PCR（RTqPCR）,the levels of TLR4,phosphorylated nuclear factor-κB（NF-κB p65） and phosphorylated extracellular signal-regulated kinase（ERK） protein in THP-1 cells by western blot,and the content of TNF-α protein in the culture supernatant of THP-1 cells by enzyme linked immunosorbent assay（ELISA）. Results 10 mg /L of fluvastatin could significantly reduce the expressions of TLR4 mRNA and protein（t = 7. 55 and 7. 80,P〈0. 05） and the levels of TNF-α mRNA and protein（q = 4. 23 and 3. 01,P〈0. 05） in THP-1 cells stimulated by LPS. 1,5 and 10 mg /L of fluvastatin could decrease the levels of NF-κB p65（q = 5. 13,6. 87 and 11. 68,P〈0. 05）and phospho-ERK（q = 11. 78,18. 15 and 18. 88,P〈0. 05） in THP-1 cells stimulated by LPS in a dose-dependent way. Conclusion Fluvastatin could inhibit the expression of TNF-α by interfering the expression of TLR4 and the phosphorylation of ERK and NF-κB,which may be one of anti-inflammatory mechanisms of fluvastatin.