亲环素A对THP-1源性泡沫细胞ABCA1表达及胆固醇流出的影响及机制

发布时间：2018-10-23 10:42

【摘要】：目的观察亲环素A(CypA)对THP-1源性泡沫细胞三磷酸腺苷结合盒转运体A1(ABCA1)表达和胆固醇流出的影响及机制。方法 160 nmol/L佛波酯诱导人THP-1单核细胞分化为巨噬细胞,与50 mg/L氧化型低密度脂蛋白(ox-LDL)共孵育,使其荷脂形成泡沫细胞,常规体外培养细胞;实验分为对照组和Cyp A处理组;液体闪烁计数仪检测细胞胆固醇流出水平,高效液相色谱检测细胞内脂质成分,实时荧光定量PCR和Western blot检测ABCA1表达,Western blot检测核因子κB(NF-κB)核转位水平;NF-κB抑制剂小白菊内酯抑制NF-κB活化;脂质体2000转染CD147 siRNA至THP-1源性泡沫细胞。结果 CypA显著抑制THP-1源性泡沫细胞胆固醇流出,促进NF-κB核转位,下调ABCA1表达;NF-κB抑制剂小白菊内酯拮抗CypA对ABCA1表达及胆固醇流出的抑制作用;用siRNA干扰CD147后,显著抑制Cyp A诱导的NF-κB核转位,上调ABCA1表达,促进胆固醇流出。结论 CypA可能通过CD147激活NF-κB,下调ABCA1表达,抑制THP-1源性泡沫细胞胆固醇流出。
[Abstract]:Aim to investigate the effect and mechanism of cyclophile A (CypA) on the expression of adenosine triphosphate binding cassette transporter A1 (ABCA1) and cholesterol efflux in THP-1 foam cells. Methods Human THP-1 monocytes were induced to differentiate into macrophages at 160 nmol/L, and incubated with 50 mg/L oxidized low density lipoprotein (ox-LDL) to form foam cells, which were cultured in vitro, and were divided into two groups: control group and Cyp A treatment group. Liquid scintillation counter was used to detect cholesterol efflux, and high performance liquid chromatography (HPLC) was used to detect lipid components in cells. Real-time fluorescence quantitative PCR and Western blot were used to detect, Western blot expression of nuclear factor 魏 B (NF- 魏 B) nuclear translocation, NF- 魏 B inhibitor chrysanthemum lactone inhibited NF- 魏 B activation, and liposome 2000 was transfected into THP-1 derived foam cells. Results CypA significantly inhibited cholesterol efflux of THP-1 derived foam cells, promoted nuclear translocation of NF- 魏 B and down-regulated ABCA1 expression, and NF- 魏 B inhibitor leucolactone antagonized the inhibition of CypA on ABCA1 expression and cholesterol efflux. SiRNA interfered with CD147. The nuclear translocation of NF- 魏 B induced by Cyp A was significantly inhibited, the expression of ABCA1 was upregulated, and cholesterol efflux was promoted. Conclusion CypA may activate NF- 魏 B through CD147, down-regulate ABCA1 expression and inhibit cholesterol efflux of THP-1 derived foam cells.
【作者单位】：邵阳学院医学院病理生理学教研室;南华大学心血管疾病研究所动脉硬化学湖南省重点实验室南华大学医学研究中心分子靶标湖南省协同创新中心;
【基金】：国家自然科学基金项目(81570408、81370377和81470569) 南华大学研究生创新课题(2016XCX04)
【分类号】：R543.5

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