环氧化酶与阿司匹林疗效的相关性研究  

The correlation between therapeutic efficacy of aspirin and cyclooxygenase

作　　者：杨蓉[1] 焦洁茹[1] 王学锋[2] 丁秋兰[2] 吴方[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院老年科,200025 [2]上海交通大学医学院附属瑞金医院临床输血科,200025

出　　处：《中华老年心脑血管病杂志》2011年第10期883-886,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：上海市科学技术委员会(074119601)

摘　　要：目的探讨环氧化酶(cyclooxygenase,COX)基因型及其表达与阿司匹林疗效的相关性。方法选择老年高血压患者181例,根据血栓弹力图分为阿司匹林敏感(aspirin sensitive group,AS)组106例,非阿司匹林敏感(notaspirin sensitive group,NAS)组75例;PCR产物直接测序分析法检测COX-1(A-842G,C22T,C50T,G128A,C644A,C714A)和COX-2(G765C)基因型;实时定量PCR及Western blot法,检测患者外周血细胞中COX-1和COX-2 mRNA及蛋白表达水平。结果 NAS组与AS组COX-1(G128A,C644A)位点突变型等位基因分布差异无统计学意义(P>0.05);与AS组比较,NAS组COX-2(G765C)位点突变型等位基因频率更高(P<0.01);而COX-1(A-842G,C22T,C50T,C714A)位点在检测人群中未发现突变型等位基因。NAS组COX-2 mRNA和蛋白表达明显高于AS组(P<0.05)。结论调查人群中COX-2(G765C)位点多态性可能与阿司匹林抵抗的发生具有相关性;COX-2表达可能是导致阿司匹林抵抗发生的原因之一。Objective To investigate the correlation between cyclooxygenase（COX） gene polymorphisms and therapeutic efficacy of aspirin. Methods The thrombelastography platelet mapping test（TEG） was performed in 181 elderly hypertensive patients who were divided into aspirin sen- sitive（AS） group 106 cases and not aspirin sensitive group（NAS） 75 cases. In these patients COX-1 （A-842G, C22T, C50T, G128A, C644A, C714A） and COX-2 （G765C） gene polymorphisms were analyzed by polymerase chain reaction and DNA sequencing assay. The COX 1 and COX-2 expression was detected by real-time PCR and Western blot in these patients. Results The fre- quencies of COX-1 （G128A,C644A） gene mutations were similar in the NAS group and the AS group（P〉0.05）,while the frequencies of COX-2（G765C） gene mutations were different（P〈 0.01）. Gene mutations of COX-1 （A-842G, C22T, C50T, C7t4A） were not found in the patients examined. COX-1 mRNA expression was not different between the NAS group and AS group, While COX-2 mRNA and protein expression was significantly higher in NAS group than in AS group（P〈0.05）. Conclusion COX-2 （G765C） polymorphism may contribute to aspirin resistance. The selective COX-2 expression may be associated with the occurrence of aspirin resistance.

关 键 词：环氧化酶1 阿司匹林 血栓弹力描记术 聚合酶链反应 基因型 

分 类 号：R96[医药卫生—药理学]