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秋水仙碱对血小板-血小板及血小板-白细胞相互作用的影响:一项在健康受试者中的初步研究。

Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects.

作者信息

Shah Binita, Allen Nicole, Harchandani Bhisham, Pillinger Michael, Katz Stuart, Sedlis Steven P, Echagarruga Christina, Samuels Svetlana Krasnokutsky, Morina Pajazit, Singh Prabhjot, Karotkin Liza, Berger Jeffrey S

机构信息

Department of Medicine, Division of Cardiology, New York University School of Medicine, 227 E 30th Street, Office 835, New York, NY, 10016, USA.

Department of Medicine, Section of Cardiology, Veterans Affairs New York Harbor Health Care System, New York, NY, USA.

出版信息

Inflammation. 2016 Feb;39(1):182-189. doi: 10.1007/s10753-015-0237-7.

Abstract

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.

摘要

秋水仙碱在稳定型缺血性心脏病患者中的心脏保护机制尚不确定。我们在体外测试了不同浓度的秋水仙碱对血小板活性的影响,并在10名健康受试者中给予了临床上相关的1.8毫克口服负荷剂量,给药时间为1小时。数据以中位数[四分位间距]表示。体外添加秋水仙碱仅在超治疗浓度下降低了透光率血小板聚集,但在治疗浓度下降低了单核细胞-血小板聚集(MPA)和中性粒细胞-血小板聚集(NPA)。对健康受试者给予1.8毫克秋水仙碱对透光率血小板聚集没有显著影响,但降低了MPA的程度(从28%[22 - 57]降至22%[19 - 31],p = 0.05)和NPA的程度(从19%[16 - 59]降至15%[11 - 30],p = 0.01),给药后2小时血小板表面PAC - 1的表达(平均荧光强度(MFI)从370[328 - 555]降至333 MFI[232 - 407],p = 0.02)和P - 选择素的表达(从351 MFI[269 - 492]降至279[226 - 364],p = 0.03),以及血小板与胶原蛋白的黏附(从10.2%[2.5 - 32.6]降至2.0%[0.2 - 9.5],p = 0.09)。因此,在临床相关浓度下,秋水仙碱可降低血小板活性表面标志物的表达并抑制白细胞 - 血小板聚集,但不抑制同型血小板聚集。

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