摘要
【目的】探讨氧化低密度脂蛋白（Ox-LDL）是否上调人单核细胞（THP-1）趋化因子Fractalkine受体CX3CR1的表达，及普罗布考、氟伐他汀干预对这种诱导表达的影响。【方法】用不同浓度的Ox-LDL刺激THP-1细胞及用不同浓度普罗布考、氟伐他汀和吡咯烷二硫代氨基甲酸酯（PDTc）预处理细胞后再用OxLDL刺激，分别用半定量RT～PCR方法检测CX3CR1以及NF-κBp65的rnRNA的表达，Western—blot测定CX3CR1、NF-KBp65的蛋白表达。【结果】①与对照组比较，Ox-LDL呈浓度依赖性诱导CX3CR1及NF-κBp65在mRNA水平及蛋白水平的表达。②普罗布考、氟伐他汀可以押制Ox-LDL诱导的上述袁达；联合用药组与单药组比较抑制Ox-LDL诱导的上述表达有显著性差异。③PDTC干预后，再用Ox-LDL刺激，与未用PDTC干预组（只用Ox-LDL刺激）比较，细胞核NF-κBp65蛋白水平明显下调（P〈0．01），但CX3CR1mR—NA和蛋白及NF-κBp65mRNA的表达均无明显下调（P〉0．05）。【结论】Ox-LDL通过NF_KB以外信号途径上调人单核细胞THP-1表达CX3CR1；PDTC可以抑制NF—κB的活化，但是不能抑制Ox-LDL上调人单核细胞THP-1表达CX3CR1；普罗布考和氟伐他汀可以抑制NF-κB的活化，亦能抑制氧化低密度脂蛋白上调人单核细胞THP-1表达CX3CR1，这种抑制作用与普罗布考和氟伐他汀抑制NF-κB的活化无关。
[Objective]To investigate the inhibitory effect of probucol and fluvastatin on the expression of CX3CR1 induced by oxidized low-density lipoprotein（Ox-LDL） in human monocyte（THP-1）. [Methods] Human THP-1 cells were incubated with different concentrations of Ox-LDL and some of them were pretreated with probucol, fluvastatin and PDTC at different concentrations, then the expression of CX3CRlmRNA and NF-κB p65mRNA were determined by semi-quantitative RT-PCR. The protein expression of CX3CR1 and NF-κB p65 were determined by western-blotting method. [Results]Compared with the control group, the expressions of CXC3R1 mRNA, NF-κB p65 mRNA, CXC3R protein and NF-κB p65 protein in human monocyte were up regulated by Ox-LDL in a concentration-dependent manner. After pretreated with probucol or fluvastatin, the expressions of CXC3R1 mRNA, NF-κB p65 mRNA, CXC3R protein and NF-κB p65 protein were inhibited significantly in a concentration-dependent manner. The combination administration of probucol and fluvastatin inhibited the expression of the above-mentioned parameters further. After THP-1 cells were pretreated by PDTC, the expression of NF-κB p65 at protein level was down-regulated. On the contrary, no remarkable effect was observed on the expression of CX3CR1 mRNA, CX3CR1 at protein level and NF-κB p65 mRNA. [Conclusion] Ox-LDL can induce the expression of CXC3R1 in THP-1 cells through NF-κB pathway. Both probucol and fluvastatin inhibit the expression of NF-κB and cXCaR1 in THP-1 cells induced by Ox-LDL, but the mechanism is not linked to the NF-κB pathway.
出处
《医学临床研究》
CAS
2010年第1期38-42,共5页
Journal of Clinical Research
