氟维司群抑制血小板功能的研究  

Study on the inhibition of platelet function by fulvestrant

作　　者：马如越 赵丽丽[2] 杨梦楠 张蕾[1] 赵瑞珩 戴克胜[1,2] Ma Ruyue;Zhao Lili;Yang Mengnan;Zhang Lei;Zhao Ruiheng;Dai Kesheng(Suzhou University Affiliated Suzhou Ninth Hospital(Suzhou Ninth People's Hospital),Suzhou 215299,China;The First Affiliated Hospital of Suzhou University,Tang Zhongying Medical Research Institute of Suzhou University,Jiangsu Institute of Hematology,Suzhou 215006,China)

机构地区：[1]苏州大学附属苏州九院(苏州市第九人民医院),苏州215299 [2]苏州大学附属第一医院,苏州大学唐仲英医学研究院,江苏省血液研究所,苏州215006

出　　处：《血栓与止血学》2024年第4期145-151,共7页Chinese Journal of Thrombosis and Hemostasis

基　　金：国家自然科学基金重点国际合作项目(81820108003);国家自然科学基金项目(81770117);苏州市吴江区卫健委科教兴卫项目(WWK202201);苏州市第九人民医院院内科研课题项目(YK202202)。

摘　　要：目的探究氟维司群对血小板功能的影响及相关机制。方法将不同浓度的氟维司群(0.1、1和10μmol/L)及溶剂对照(0.25%二甲基亚砜DMSO)分别与人血小板在体外进行共孵育,然后用聚集仪检测其对凝血酶、胶原、U46619刺激的血小板聚集及ATP释放的影响;流式细胞术检测血小板表面P-选择素表达和整合素αIIbβ3活化情况;荧光显微镜观察氟维司群对纤维蛋白原表面血小板铺展的影响;蛋白免疫印迹检测AKT Ser473和PKC蛋白的磷酸化水平。结果氟维司群能够抑制凝血酶、胶原、U46619诱导的血小板聚集和ATP释放,抑制血小板P-选择素表达和整合素αIIbβ3活化和血小板铺展,降低AKTSer473和PKC的磷酸化水平。结论氟维司群抑制血小板聚集、释放、铺展功能,其机制与调控AKT和PKC蛋白磷酸化水平有关,可作为潜在的抗血小板药物。Objective To investigate the effect of fulvestrant on platelet function and its related mechanism.Methods Different concentrations of fulvestrant(0.1,1 and 10μmol/L)and solvent control(0.25% dimethyl sulfoxide(DMSO))were co⁃incubated with human platelets in vitro,and then the effects of fulvestrant on platelet aggregation and ATP release stimulated by thrombin,collagen and U46619 were detected by aggregometer.The expression of P⁃selectin on the platelet surface and the activation of integrin αIIbβ3 were detected by flow cytometry.The effect of fulvestrant on platelet spreading on the fibrinogen surface was observed by fluorescence microscopy.The phosphorylation levels of AKT Ser473 and PKC proteins were detected by western blotting.Results Fulvestrant could inhibit platelet aggregation and ATP release induced by thrombin,collagen and U46619,inhibit the expression of P-selectin,integrinαIIbβ3 activation and platelet spreading,and reduce the phosphorylation levels of AKT Ser473 and PKC.Conclusion Fulvestrant inhibits platelet aggregation,release and spreading,and its mechanism is related to the regulation of AKT and PKC protein phosphorylation levels.It can be used as a potential antiplatelet drug.

关 键 词：氟维司群 血小板活化 AKT磷酸化 PKC通路 

分 类 号：R331.143[医药卫生—人体生理学]