瑞舒伐他汀预处理对外周血树突状细胞的影响  

Effect of pretreatment with rosuvastatin on dendritic cells of peripheral blood

作　　者：王航[1] 黄浩[2] 蔡克银[1] 

机构地区：[1]广州军区武汉总医院干部病房二科,430070 [2]华中科技大学同济医学院附属协和医院消化内科

出　　处：《中华老年心脑血管病杂志》2010年第10期935-939,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

摘　　要：目的探讨瑞舒伐他汀对树突状细胞（dendritic cells，DCs）成熟程度及其功能的影响。方法体外分离培养外周血单核来源的DCs，第一部分给予不同剂量的瑞舒伐他汀预处理24h，依次分为他汀1摩组、他汀5摩组、他汀10摩组和他汀15摩组；第二部分不同时间给予10μmol／L瑞舒伐他汀预处理依次为他汀1h组、他汀12h组、他汀24h组、他汀36h组；第三部分选用10μmol／L瑞舒伐他汀作用36h为预处理组；各组均用TNF-α诱导DCs成熟的方式，三部分实验中，PBS预处理为空白组，仅加TNF-α处理为对照组，用流式细胞仪检测各组DCs表面分子CD86、CD83、CD40、HLA～DR、CD80的表达，用ELISA法检测DCs分泌的趋化因子，^3H胸腺嘧啶核苷掺入法检测DCs诱导自体T淋巴细胞增殖反应。Western blot法检测DCs细胞质NF-κB抑制蛋白（IκBα）、NF-κB表达。结果与对照组比较，不同浓度和不同时间作用组CD86表达均有下降趋势；经终浓度10μmol／L瑞舒伐他汀处理36h后DCs表面分子CD83、CD40、CD86、HLA—DR、CD80均有不同程度的下调，上清液中MCP-1浓度以及DCs促T淋巴细胞增殖的作用明显下降（P〈0．01）。Western blot检测表明，瑞舒伐他汀预处理后各组，IκBα表达均有不同程度增加，NF-κB含量则存在不同程度的减少，并表现一定的剂量和作用时间的依赖性，但当剂量达到10μmol／L，作用时间为24h时，作用达到一个平台期。结论瑞舒伐他汀预处理可以抑制外周血单核来源的DCs成熟，并影响DCs的促T淋巴细胞增殖能力及迁移能力。Objective To investigate the effects of rosuvastatin on maturation and function of dendritic cells （DCs） derived from peripheral blood mononuclear cells （PBMCs）. Methods PBMCs from healthy donors were cultured. Experiment Ⅰ ,PBMCs were treated with rosuvastatin at different dosages for 24 hours. Experiment Ⅱ , PBMCs were treated with 10μmol/L rosuvastatin for 1--36 hours. Experiment Ⅲ,PBMCs were treated with 10 μmol/L rosuvastatin for 36 hours. TNF-α was used to induce maturation of DCs. Flow cytometry was used to analyse the cell surface markers of DCs. ^3H-TdR incorporation was used to measure the stimulating effect of DCs on the syngeneic and allogeneic T cells. ELISA was used to measure secretion of MCP-1 and MIP1 of DCs. Western blot analysis was used to evaluate expression of IκBα and NF-κB in DCs. Results Addition of rosuvastatin could downregulate the cell surface markers including CD40, CD83, HLA-DR,CD80 and CD86, reduce the secretion of MCP-1 and stimulation to allogeneic T cells. Both degradation of IκBα and expression of NF-κB were decreased in DCs. These changes could be amplified with increase of dosage and reached max at 10 μmol/L. These changes also could be amplified with increase of action time and reached max at 24 hours. Conclusion Rosuvastatin can inhibit the maturation of DCs,which may be realized through degradation of IκBα in DCs.

关 键 词：氟苯类 羟甲基戊二酰基COA还原酶抑制剂 树突细胞 NF-ΚB 瑞舒伐他汀 

分 类 号：R96[医药卫生—药理学]