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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

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【作者】 郭玥; 庄晓东; 李菲菲; 杜志民;

【Author】 GUO Yue;ZHUANG Xiao-dong;LI Fei-fei;DU Zhi-min;Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University;

【机构】 中山大学附属第一医院心内科;

【摘要】 【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。

【Abstract】 【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.

【基金】 国家自然科学基金(81270296);广东省科技厅项目(2010B031600056)
  • 【文献出处】 中山大学学报(医学科学版) ,Journal of Sun Yat-sen University(Medical Sciences) , 编辑部邮箱 ,2015年03期
  • 【分类号】R965
  • 【被引频次】7
  • 【下载频次】209
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