辛伐他汀对人单核源树突状细胞成熟及免疫功能影响的研究

On effects of simvastatin on human monocyte derived DCs mature and its on immunological functions

目的:探讨辛伐他汀对人单核源树突状细胞(Dendritic cell,DC)成熟和免疫功能的影响。方法:梯度离心法分离人外周血单核细胞(peripheral blood monouclear cells,PBMC),经含重组人粒细胞-巨噬细胞集落刺激因子(recombinant human granulocyte-macrophage colony-stimulating factor,rhGM-CSF)和重组人白介素-4(recombinant human interleukin-4,rhIL-4)的Cellgro培养,使其分化为DC。以PBS组作阴性对照,LPS组作阳性对照,将DC与Dil染料标记的氧化低密度脂蛋白共同孵育48 h及DC与100μmol/L辛伐他汀和50 mg/L DiI染料标记的氧化低密度脂蛋白(oxy-Low Density Lipoprotein,0x-LDL)共同孵育48 h作实验组,流式细胞术(Fluorescence Activated Cell Sorting,FACS)检测DC表型(CDla、CD80、CD86、HLA-DR)的表达,同时镜下观察DC吞噬0x-LDL的形态变化。结果:经辛伐他汀处理的DC可下调CDla、HLA-DR的表达,抑制DC对0x-LDL的吞噬作用。结论:辛伐他汀可明显抑制DC的免疫活性,他汀类药物可能具有免疫调节的新机制。

Objective： To investigate the effects of simvastatin on human monocyte derived DCs mature and its on immunological functions. Methods： Human monoeytes were isolated by means of gradient centrifugatinn method, followed by 5 days＇ culture with DC Cellgro medium containing 100ng/ml rhGM -CSF and 20ng/ml rhlL- 4. Mature DCs was then obtained. DBS and LPS were as the negative and positive control, and in experimental groups, antigen as Ox - LDL labelled with 50 μg/mlDil were added to the medium both to iucubate with DCs, while drug as 100 μmol/L simvastatin was only added to one group. FACS was used to investigate the immuno - phenotypic expression（ CDI a, CD50, CD86 and HLA - DR） after 48 hours. The progress of phagocytosis was observed in microscope, and the effects of DCs on lymphocyte proliferation was observed by mixed T lymphocyte reaction. Results： Atorvastatin reduced DCs＇ immuno - phenotypic expressions of CD 1 a and HLA - DR, and inhibited DCs＇ Phagocytosis of 0x - LDL. Conclusion： Simvastatin can significantly inhibit immune activity and the function of phagocytosis of DCs, which shows a new immune regulating mechanism of statins series.