阿托伐他汀对大鼠树突状细胞吞噬功能及共刺激分子表达的影响

摘要

目的 探讨阿托伐他汀对大鼠单核细胞源性树突状细胞(DCs) 吞噬功能及表面共刺激分子表达的影响.方法 密度梯度离心法分离大鼠外周血单个核细胞,经含重组鼠粒细胞-巨噬细胞集落刺激因子(rmGM-CSF)100 ng/mL、重组鼠白介素-4(rmIL-4)20 ng/mL的完全RPMI 1640培养基培养,使其分化为DCs.以磷酸盐缓冲液(PBS)组作阴性对照,将DCs与50 μg/mL 1,1′二(十八烷基) 3,3′,3′,3′四甲基吲哚羰基花青高氯酸盐(DiI)染料标记的氧化低密度脂蛋白(ox-LDL)共同孵育48 h(加或不加100 μmol/L阿托伐他汀)作为实验组,流式细胞术检测DCs表面共刺激分子CD86、CD40的表达,同时镜下观察DCs吞噬ox-LDL的形态变化.结果 ox-LDL上调DCs表面共刺激分子CD86、CD40的表达,经阿托伐他汀处理的DCs可下调CD86、CD40的表达,对ox-LDL的吞噬作用受到抑制.结论 阿托伐他汀可明显抑制DCs的吞噬功能及表面共刺激分子表达.%Objective To investigate the effects of atorvastatin on phagocytosis and co stimulatory factor of monocyte derived dendritic cells(DCs). Methods Density gradient centrifugation was used to isolate peripheral blood mononuclear cell from rats.DCs were derived from monocytes of mice upon culturing with rmGM-CSF(100 ng/mL) and rmlL-4(20 ng/mL). PBS was as the negative control,and in two experimental groups,antigen as ox LDL labelled with 50 μg/ml DiI were added into the medium in cubating with DCs,while 100 μmol/L atorvastatin was only added to one group. Surface co stimulatory factors CD86 and CD40 of DCs were measured by flow cytometry after 48 hours. The progress of phagocytosis was observed in microscope. Results ox LDL upregulated expression of surface co stimulatory factors CD86 and CD40 of DCs. Atorvastatin reduced expression of surface costimulatory factors CD86 and CD40 of DCs,and inhibited DCs phagocytosis of ox LDL. Conclusion Atorvastatin significantly in hibits immune activity and the function of phagocytosis of DCs,vhich may be a new immune regulating mechanism of statins series.