摘要： 研究背景 抗血小板治疗已经成为缺血性卒中的常规治疗方法，目前对其作用的肯定主要源于临床应用，迄今尚无一项能够准确评价其有效性的实验室指标。有研究证实，血小板活化程度与动脉粥样硬化和缺血性卒中相关，尤其是血小板α颗粒膜糖蛋白CD62p 和溶酶体膜糖蛋白CD63 均为血小板活化的重要指标。本研究旨在通过观察急性缺血性卒中患者血小板膜表面CD62p 和CD63 表达变化，探讨以血小板活化程度反映氯吡格雷（75 mg）、奥扎格雷钠（80 mg）与阿司匹林（0.15 g）的疗效差异。方法 采用流式细胞术检测急性缺血性卒中患者氯吡格雷（75 mg）联合奥扎格雷钠（80 mg，联合治疗组）及阿司匹林单药（阿司匹林组）治疗前后血小板CD62p 和CD63 阳性表达率，美国国立卫生研究院卒中量表（NIHSS）评价神经功能改善程度。结果 与正常对照组相比，治疗前急性缺血性卒中组患者血小板CD62p 和CD63 阳性表达率升高（P = 0.001，0.032）；治疗后CD62p 和CD63 阳性表达率、NIHSS 评分逐步下降（均P = 0.000）。与治疗前相比，治疗后联合治疗组和阿司匹林组患者血小板CD62p 和CD63阳性表达率、NIHSS 评分逐步下降（均P = 0.000），但组间差异无统计学意义（均P > 0.05）。CD62p 和CD63 阳性表达率在不同观察时间点与治疗分组之间不存在交互作用（F = 1.403，P = 0.250；F = 2.830，P = 0.063），但NIHSS 评分在不同观察时间点与治疗分组之间存在交互作用（F = 4.518，P = 0.013）。结论 抗血小板药物治疗急性缺血性卒中有效，但氯吡格雷与奥扎格雷钠联合治疗之疗效与阿司匹林单药治疗并无差异。缺血性卒中急性期测定血小板CD62p 阳性表达率可以用于评价抗血小板药物的疗效，但CD63表达的临床价值尚待进一步研究。

关键词: 噻氯匹定（氯吡格雷）, 甲基丙烯酸盐（奥扎格雷钠）, 阿司匹林, 脑缺血, 血小板膜糖蛋白类, 血小板活化, 流式细胞术

Abstract: Background  Antiplatelet aggregation treatment has become a regular treatment of ischemic stroke. The affirmation of antiplatelet therapy is mainly derived from patients with clinical use, which can not provide the laboratory indexes for evaluation of a recognized accuracy. Studies have confirmed that the degree of platelet activation is associated with atherosclerosis and ischemic stroke, and recognized that both CD62p (α-platelet granule membrane glycoprotein) and CD63 (lysosomal membrane glycoprotein) were important indexes of platelet activation. This study aims to explore the differences of efficacy between combined use of clopidogrel and ozagrel sodium and monotherapy by aspirin in the treatment of acute ischemic stroke by investigating the expression of CD62p and CD63.  Methods  Flow cytometry was employed to detect CD62p and CD63 expression on circulating platelet in patients with ischemic stroke and normal control group. The positive rate of CD62p and CD63 was detected in patients with ischemic stroke who were treated with aspirin 0.15 g (single drug therapy) and clopidogrel 75 mg + ozagrel sodium 80 mg (combination therapy) before and after one and two weeks' treatment. National Institute of Health Stroke Scale (NIHSS) scores were measured in patients with ischemic stroke at the same time in three periods respectively to evaluate the improvement of neural function.  Results  Platelet CD62p and CD63 positive expression rate in ischemic stroke group were higher than normal control group before treatment (P = 0.001, 0.032). CD62p and CD63 positive expression rate and NIHSS score were measured at different times, and the differences were statistically significant (F = 56.693, P = 0.000; F = 21.544, P = 0.000; F = 216.271, P = 0.000, respectively). Compared with before treatment, CD62p and CD63 positive expression rate and NIHSS score decreased significantly after treatment (P = 0.000, for all), but the differences between aspirin group and combination group were not statistically significant (P > 0.05, for all). There was no interaction between the treatment groups and measuring time with CD62p and CD63 positive expression rate (F = 1.403, P = 0.250; F = 2.830, P = 0.063), while there was interaction between treatment groups and measuring time with NIHSS score (F = 4.518, P = 0.013).  Conclusion  Antiplatelet drug treatment of acute ischemic stroke is effective. The curative effect of combined treatment (clopidogrel and ozagrel sodium) is not superior to aspirin alone. CD62p positive expression rate in acute stage of ischemic stroke can measure the effect of antiplatelet therapy, while the determination of CD63 needs further research.

Key words: Ticlopidine (Clopidogrel), Methacrylates (Ozagrel sodium), Aspirin, Brain ischemia, Platelet membrane glycoproteins, Platelet activation, Flow cytometry