新型抗血小板药物替格瑞洛对鼠树突状细胞免疫功能的影响

Immunosuppressive Effect of Ticagrelor, a Novel Antiplatelet Drug, on Dendritic Cell Function

【目的】研究体外实验中,抗血小板药物替格瑞洛对原代小鼠树突状细胞(DC)摄取吞噬抗原以及促进T细胞增殖能力的影响。【方法】以RT-PCR、Western-Blotting方法测定细胞P2Y12受体基因和蛋白水平表达。实验分为空白对照组、单纯ADPβS刺激组、替格瑞洛+ADPβS组。以FITC标记葡聚糖(FITC-Dextran)作为荧光抗原检测DC吞噬抗原能力;将DC负载卵清蛋白(OVA),与OT-2转基因鼠脾脏T淋巴细胞共培养4 d,流式细胞仪检测荧光染料CFSE标记T细胞增殖情况。【结果】小鼠DC上表达P2Y12受体。替格瑞洛能够阻断ADPβS诱导的DC抗原吞噬功能(P<0.05),以及显著抑制T细胞增殖能力(P<0.05)。【结论】抗血小板药物替格瑞洛可以通过P2Y12受体抑制鼠DC免疫功能,发挥免疫调节作用,为冠心病治疗提供新的途径。

[Objective] This study aims to investigate the in vitro effects of ticagrelor on Ag endocytosis and presentation by dentritic cells （DC）,thereby exploring the role of ticagrelor in immune regulation.[Methods] P2Y12 expression in DC was analyzed by RT-PCR and Western-blotting.DC were divided into normal culture group,simple ADPβS group and ticagrelor ＋ ADPβS group.Fluorescein isothiocyanate （FITC）-Dextran was used to test DC endocytosis.Ovalbumin （OVA）-specific T （OT-2） cells were purified from the spleen.The carboxyl fluorescein succinimidyl ester （CFSE）-labeled T cells were co-cultured with OVA-loaded DC for 4 d,and T cell proliferation was analyzed by flow cytometry.[Results] RT-PCR and Western blot analysis revealed expression of functional P2Y12 receptors in murine DC.Ticagrelor blocked ADPβS-induced DC endocytosis,and significantly diminished the ability of DC to simulate Ag-specific T cells.[Conclusion] Our study demonstrates that antiplatelet drug ticagrelor directly inhibits DC function via P2Y12 receptors,which is probably beneficial for treatment of coronary heart disease.