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氯吡格雷和阿司匹林对马血小板聚集、血栓素生成和 5-羟色胺分泌的影响。

Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses.

机构信息

Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.

出版信息

J Vet Intern Med. 2011 Jan-Feb;25(1):116-22. doi: 10.1111/j.1939-1676.2010.0647.x. Epub 2010 Dec 8.

Abstract

BACKGROUND

Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation.

OBJECTIVES

To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function.

ANIMALS

Six healthy adult horses.

METHODS

Horses received clopidogrel (2 mg/kg p.o. q24h) or ASA (5 mg/kg p.o. q24h) for 5 days in a prospective randomized cross-over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B(2) (TXB(2) ) by ELISA were evaluated. In horses receiving clopidogrel, high-performance liquid chromatography analysis for clopidogrel and its carboxylic-acid metabolite SR 26334 was performed.

RESULTS

SR 26334 was identified in all clopidogrel-treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP-induced platelet aggregation persisting for 120 hours after the final dose. ADP-induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P < .001). Collagen-induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB(2) from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P < .01).

CONCLUSIONS AND CLINICAL IMPORTANCE

Clopidogrel effectively decreases ADP-induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.

摘要

背景

危重病马易患血栓性疾病,这可能与血小板反应性和激活增加有关。

目的

比较口服氯吡格雷和阿司匹林(ASA)对马血小板功能的影响。

动物

6 匹健康成年马。

方法

采用前瞻性随机交叉设计,马连续 5 天口服氯吡格雷(2mg/kg,q24h)或 ASA(5mg/kg,q24h)。通过光学聚合仪评估对二磷酸腺苷(ADP)和胶原蛋白的血小板聚集反应,通过 ELISA 评估血小板 5-羟色胺(5HT)分泌和血栓素 B2(TXB2)生成。在接受氯吡格雷治疗的马中,进行高效液相色谱分析以检测氯吡格雷及其羧酸代谢物 SR 26334。

结果

在所有接受氯吡格雷治疗的马中均检测到 SR 26334,尽管未检测到母体化合物。氯吡格雷导致 ADP 诱导的血小板聚集在最后一次给药后 120 小时内持续降低。ADP 诱导的血小板聚集从基线的 70.2±14.7%降低至最后一次给药后 24 小时的最小 15.9±7.7%(P<.001)。胶原诱导的聚集从基线的 93±9.5%降低至最后一次给药后 48 小时的最小 70.8±16.9%(P<.001)。ASA 不能降低两种激动剂诱导的血小板聚集。ASA 在 24 小时内将血清 TXB2 从基线值 1310±1045 降低至 128±64pg/mL(P<.01)。

结论和临床意义

氯吡格雷可有效降低马 ADP 诱导的血小板聚集,可能对与血小板激活相关的马疾病具有治疗应用价值。

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