抗血小板药物对TIA患者CD62p和PAC-1表达率的作用

Study on the effectiveness of antiplatelet drugs in inhibiting platelet activation in patients with transient ischemic attack

目的观察短暂性脑缺血发作(TIA)患者血小板活化状态的改变。探讨TIA患者应用氯吡格雷、阿司匹林和缓释双嘧达莫3种抗血小板药物治疗对血小板活化抑制作用的机制,比较3种药物联用和单用的不同效果。方法选择年龄在40岁以上初入院的TIA患者60例作为试验组,随机分为3组,每组20例。第一组患者分别给予缓释双嘧达莫200 mg和阿司匹林25 mg,2/d;第二组患者分别给予氯吡格雷75 mg和阿司匹林80 mg,1/d;第三组患者给予氯吡格雷75 mg,1/d,同时随机抽取40岁以上健康体检者30名作为对照组。采用流式细胞技术分别检测对照组和3个试验组患者入院治疗前、治疗7 d和治疗15 d后的血小板活化标志物P-选择素(CD62p)和血小板膜暴露纤维蛋白原受体(PAC-1)的表达率,并比较3组药物对血小板活化的抑制作用。结果与健康对照组相比,TIA患者各试验组初入院时血小板活化标志物CD62p和PAC-1表达均升高,但各试验组间没有明显差别。3组抗血小板药物对TIA患者血小板活化标志物CD62p和PAC-1表达的抑制作用明显不同。第一组在治疗7 d后对血小板PAC-1没有明显抑制作用,只对血小板CD62p有明显的抑制作用,而治疗15 d后能明显抑制血小板CD62p和PAC-1的表达;第二组在治疗7 d和15 d后抑制血小板PAC-1表达的作用显著,但对CD62p表达的抑制作用较小;第三组单独给药比第二组联合用药的抑制作用明显减弱。结论 TIA患者血小板活化状态明显高于健康人。在TIA患者中,3组药物对血小板活化的抑制方式不同。缓释双嘧达莫+阿司匹林是治疗TIA、抑制血小板CD62p和PAC-1表达的有效药物,但其作用效果呈明显的时间依赖性。

Objective To observe the changes of platelet activation status in patients with transient ischemic attack（TIA）. To study the action of clopidogrel,aspirin（ASA） and the combination of extended release dipyridamole（ER-DP） and ASA in inhibiting platelet activation in patients with TIA. To compare the different effects to ER-DP ＋ ASA and clopidogrel with or without ASA in pa-tients with TIA. Methods Sixty eligible patients who had been diagnosed with TIA and were over the age of 40 were randomly se-lected. They were divided into three groupsof twenty. Patients from the first group received ER-DP 200 mg/d plus ASA 25 mg BID,patients from the second group received clopidogrel 75 mg/d plus ASA 80 mg/d and patients from the third group received clopidogrel75 mg/d. 30 health controls were selected. The expression of the platelet activation markers CD62 p and PCA-1 were assessed before treatment,on day 7 and day 15 using flow cytometry. The effects of the three kinds of anti-platelet drugs on inhibiting platelet activa-tion were observed and compared. Results The expression of platelet activation markers CD62 p and PAC-1 of TIA test group was significantly higher than that of the healthy group. There were no differences between three test groups of TIA inpatients. There were significant differences between three kinds of anti-platelet drugs in inhibiting the expression of CD62 p and PAC-1.7 days after treat-ment,the combination of extended-release dipyridamole and aspirin（the first test group） could markedly inhibit the expression of CD62 p instead of PAC-1. However,the first test group could markedly inhibit the expression of CD62 p and PAC-1 of the platelets after treatment 15 days. The addition of ASA to clopidogrel was associated with significant inhibition of PAC-1 on days 7 and 15,but there was less inhibition in the expression of CD62 p. Compared with the second test group,there was significant reduction in inhibiting platelet activation in the clopidogrel monotherapy group. Conclusion TIA patients show a much higher expression of platelet activation than the healthy people. In these patients with TIA,patterns of platelet activation inhibiton differs significantly according to whether the treatment was with ER-DP plus ASA or clopidogrel with or without ASA. The antiplatelet effect of ER-DP plus ASA is more potent and time-dependent. It plays an important role in preventing and treating TIA.