缺血性脑卒中患者抗血小板药物治疗抵抗与环氧化酶-1基因多态性的关系

Antiplatelet drug resistance in ischemic stroke patients and its correlation to COX-1 gene

目的研究老年缺血性卒中患者中阿司匹林抵抗的发生率及其发生的机制,进一步研究阿司匹林联合氯吡格雷双重抗血小板治疗的疗效。方法从老年缺血性脑卒中患者共86例患者中筛选出AR患者14例和AS患者40例,选取16例做为AS组。所有患者口服拜阿司匹林100mg、氯吡格雷75mg,每日1次;分别于治疗1w、2w及4w后,测定各组PAG和尿11-DH-TXB2,比较各组PAG和尿11-DH-TXB2的变化以及COX-1基因多态性。结果治疗前AS组PAG比例和尿11-DH-TXB2水平均较AR组高,差异有统计学意义;治疗后AS组水平显著下降,与AR组相比,没有统计学意义。COX-1基因709C/A多态性检测。发现GG、AG和AA 3种基因型频率AS组分别为68.75%、44.4%和25%,AR组分别为14.63%、51.22%和34.15%,两组比较差异有统计学意义(χ2=30.7,P=0.000)。结论 709C/A基因多态性可能与阿司匹林抵抗性相关;阿司匹林和氯吡格雷双重抗血小板药物治疗缺血性卒中可以显著降低AR的发生率,两者联用具有协同抗血小板作用。

Objective To investigate the prevalence of aspirin resistance and its relationship with eyelooxygenase-1 （ COX-1 ） gene in elderly patients with isehemie stroke. Methods We recruited 86 elderly patients with isehemic stroke in this study. They were divided into aspirin resistance （AR） group（n = 14） or aspirin sensitive（AS）group （n=16） accord- ing to the platelet activity determined by whole blood aggregometry. All the patients take daily doses of aspirin 100mg and clopidogrel 75rag. PAG and 11-DH-TXB2 were checked after at 1,2 and 4 weeks, and the COX-1 gene polymorphism was genotyped. Results There was a relationship between COX-1 gene 709C/A single nucleotide polymorphism and antiplatelet resistance. Aspirin combined with clopidogrel has significant effect for patients with aspirin resistance to prevent isehemic stroke. Conclusion 709C/A polymorphism may be associated with aspirin resistance related;aspirin and elopidogrel dual antiplatelet therapy for ischemic stroke, can significantly reduce the incidence of AR, both combined with a synergistic anti- platelet effect.