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

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。

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

Objective: To investigate the effects of simvastatin on human monocyte derived DCs mature and its on immunological functions.Methods: Human monocytes were isolated by means of gradient centrifugation 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.PBS and LPS were as the negative and positive control,and in experimental groups,antigen as 0x-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,CD80,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 l 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.