论文部分内容阅读
目的:研究细胞亲环素A对单核来源泡沫细胞功能的影响,探讨细胞亲环素A(CypA)在动脉粥样硬化发病过程中的作用。方法:以氧化型低密度脂蛋白诱导,建立人单核细胞系(THP-1细胞)分化的泡沫细胞模型,采用油红O染色进行形态学鉴定。以不同浓度的重组人CyPA(50、100、200μg/L)刺激人单核来源的泡沫细胞,通过细胞黏附实验、基质侵袭实验和明胶酶谱实验检测在分化的过程中CypA作用前后,MMP的表达,细胞黏附和侵袭力的变化。进而用环孢素A(CsA)、HAb18 mAb、c7b8 f10以及HAb18 mAb联合c7b8 f10分别进行阻断实验,观察对泡沫细胞功能的抑制作用。结果:在单核向泡沫细胞分化的各阶段中,泡沫细胞MMP-2、9的表达,黏附基质和侵袭能力均较THP-1单核株和巨噬细胞显著增强(P<0.05);CyPA对泡沫细胞上述功能有促进作用,浓度100~200μg/L的作用效果最明显(P<0.05);以上拮抗剂均可不同程度阻断CypA作用于泡沫细胞前后的上调作用,其中以HAb18 mAb联合c7b8 f10的抑制作用最明显(P<0.05)。结论:CypA上调了动脉粥样硬化泡沫细胞MMP-2、9的表达及其活性,增强了泡沫细胞黏附、侵袭能力,其促进作用可被CypA和CD147的拮抗剂所抑制。这一作用机制可能与动脉粥样硬化斑块不稳定性的发病机制相关联,并为其治疗提供了新的理论基础。
Objective: To investigate the effect of cyclophilin A on the function of monocyte-derived foam cells and to explore the role of cyclophilin A (CypA) in the pathogenesis of atherosclerosis. Methods: The foam cell model of human monocytic (THP-1) cell line was induced by oxidized low density lipoprotein (LDL) and identified by oil red O staining. Human monocyte-derived foam cells were stimulated with different concentrations of recombinant human CyPA (50, 100, 200 μg / L). The cell adhesion assay, matrix invasion assay and gelatin zymography were used to detect the expression of MMP Expression, cell adhesion and invasiveness changes. Furthermore, CsA, HAb18 mAb, c7b8 f10 and HAb18 mAb combined with c7b8 f10 were respectively used for blocking experiments to observe the inhibitory effect on foam cell function. RESULTS: The expression of MMP-2, MMP-2, MMP-2, MMP-2 and MMP-2 in foam cells were significantly higher than those in THP-1 monocytes and macrophages (P <0.05) (P <0.05). The above antagonists could block the up-regulation of CypA before and after foam cells to varying degrees, of which HAb18 mAb combined The inhibitory effect of c7b8 f10 was the most significant (P <0.05). CONCLUSION: CypA up-regulates the expression and activity of MMP-2, MMP-2 and MMP-2 in atherosclerotic foam cells, and enhances the adhesion and invasion ability of foam cells. CypA and CD147 antagonists can inhibit this effect. This mechanism of action may be associated with the pathogenesis of atherosclerotic plaque instability and provide a new rationale for its treatment.