阿司匹林抗血小板聚集的监测和机制研究

发布时间：2018-04-05 22:15

本文选题：阿司匹林　切入点：血小板聚集　出处：《世界临床药物》2016年02期

【摘要】：目的探究腺苷二磷酸(ADP)监测阿司匹林抗血小板聚集的作用及相关的信号转导通路,为抗血小板聚集药物的筛选提供指导。方法 SD大鼠灌胃给药(0.5%CMC-Na,5 ml/kg;阿司匹林20、50和100 mg/kg;普拉格雷25 mg/kg),均为一日1次,共4 d。最后一次给药后1 h,大鼠经水合氯醛麻醉,腹主动脉采血,低速离心,收集上层液(富血小板血浆)。应用不同浓度(0、0.1、0.3、1和10μmol/L)的ADP对阿司匹林抗血小板聚集的作用进行监测。利用富血小板血浆进行蛋白质印迹试验,观察相关蛋白激酶的激活情况。结果不同剂量阿司匹林对ADP诱导血小板聚集的抑制率随着ADP浓度的增加(0~10μmol/L)呈先升高后降低的趋势,这种现象与阿司匹林剂量无关。在ADP浓度为0.3μmol/L时,阿司匹林低(20 mg/kg)、中(50 mg/kg)及高剂量(100 mg/kg)组的血小板聚集抑制率均为同组中最高(与阴性对照组比较,P0.01)。而在ADP浓度为10μmol/L时,阿司匹林的血小板聚集抑制率均小于10%,对应普拉格雷组(25 mg/kg)的血小板聚集抑制率为(76.72±7.83)%;蛋白质印迹试验结果表明,不同剂量阿司匹林均可引起ERK2显著磷酸化,且ERK2磷酸化程度随阿司匹林剂量的增加有减弱趋势。结论低剂量ADP(0.3μmol/L)用于监测阿司匹林的抗血小板聚集作用更为可靠。
[Abstract]:Objective to investigate the role of Aspirin in antiplatelet aggregation and its signal transduction pathway in order to provide guidance for the screening of antiplatelet aggregation drugs.Methods Sprague-Dawley rats were given 0.5 ml / kg CMC-NaOH, 50 mg / kg aspirin and 100 mg / kg aspirin, and 25 mg / kg Pragray once a day for 4 days.One hour after the last administration, rats were anesthetized by chloral hydrate, blood was collected from abdominal aorta, centrifuged at low speed, and the supernatant (platelet-rich plasma) was collected.The antiplatelet effect of aspirin on platelet aggregation was monitored by ADP with different concentrations of 0.1 渭 mol / L and 10 渭 mol / L of Aspirin.The activation of protein kinase was observed by Western blotting assay with platelet rich plasma.Results the inhibitory rate of different doses of aspirin on platelet aggregation induced by ADP was increased first and then decreased with the increase of ADP concentration, which was independent of the dose of aspirin.When the concentration of ADP was 0.3 渭 mol/L, the inhibition rate of platelet aggregation was the highest in the group of 20 mg / kg Aspirin, 50 mg / kg Aspirin and 100 mg / kg of high dose of Aspirin (compared with the negative control group (P 0.01).When the concentration of ADP was 10 渭 mol/L, the inhibition rate of platelet aggregation of aspirin was less than 10. The inhibition rate of platelet aggregation was 76.72 卤7.83% in the Pragray group (25 mg / kg). The results of Western blot showed that different doses of aspirin could induce the phosphorylation of ERK2.The degree of phosphorylation of ERK2 decreased with the increase of aspirin dosage.Conclusion low dose ADP(0.3 渭 mol / L is more reliable for monitoring the antiplatelet aggregation of aspirin.
【作者单位】：中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室;
【基金】：上海市浦江人才计划(编号:13PJ1433100) 留学人员科技活动项目资助上海市生物物质成药性评价专业技术服务平台(编号:15DZ2291700)
【分类号】：R965

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