【作者】 侯靓亮；

【导师】 魏立；

【作者基本信息】 青岛大学 ， 内科学， 2010， 硕士

【摘要】 多项临床试验证明,阿司匹林用于心脑血管血栓栓塞性疾病的一级以及二级预防,能够有效地预防心肌梗死、脑卒中以及心血管死亡的发生。其通过不可逆抑制血栓素A2 (TXA2)的合成发挥抑制血小板聚集的作用。但临床发现,有部分患者正规服用阿司匹林后仍出现血栓栓塞事件,即阿司匹林抵抗现象(Aspirin Resistance,AR)。本研究旨在观察阿司匹林抵抗的发生率,相关危险因素,及其与血小板P-选择素之间的相关性。方法入选冠心病患者50例(男26例,女24例),测定干预前P-选择素水平,给予阿司匹林100mg 1/晚连续口服2周,比浊法测定血小板聚集率,分为抵抗及敏感(Aspirin Sensitive, AS)两组,测定干预后P-选择素(P-selection, P-选择素)表达。结果本研究AR的发生率为18%(9/50),男女无明显差异(P=0.385)。AR与AS两组患者间低密度脂蛋白水平(3.65±1.17 vs 2.93±1.03,P=0.018)、高血压患病率(66.7%vs 29.2%,P=0.03)、总胆固醇水平(5.43±1.6 vs 5.09±1.63,P=0.042)及血红蛋白水平(130±7.9 vs 139±14.75,P=0.05)均有显著差异。Logistic多元回归分析则显示,低密度脂蛋白水平(OR=3.26)及高血压(OR=3.89)是阿司匹林抵抗的独立危险因素(P<0.05)。两组患者服药后血小板P-选择素表达有显著性差异,AR组患者服药后血小板P-选择素水平显著高于AS组(2.97±1.64 vs 2.48±1.01,P=0.003)。阿司匹林干预前,AR与AS组P-选择素水平无显著差异(3.36±1.55 vs3.34±1.10,P=0.982),干预后则有显著差异(2.97±1.64 vs 2.48±1.01,P=0.003)。在AR组,干预前后P-选择素水平无明显差异(3.36±1.55 vs 2.97±1.64,P=0.08),在AS组,干预前后P-选择素水平有明显差异(3.34±1.10 vs 2.48±1.01,P=0.03)。AR组干预后P-选择素与血小板聚集率呈正相关(r=0.472,P=0.037),而AS组干预后P-选择素与血小板聚集率无明显相关性(r=0.014,P=0.931)。结论阿司匹林抵抗的发生率为18%,在男、女性别无显著差异。低密度脂蛋白水平和高血压是发生阿司匹林抵抗的独立危险因素,而与患者年龄、体重、血糖、血小板、白细胞、血红蛋白等指标均无显著相关性。阿司匹林通过不可逆乙酰化环氧合酶-1,抑制TXA2合成,从而抑制血小板活化的同时间接抑制血小板表面P-选择素的表达。血小板P-选择素表达与阿司匹林抵抗之间呈正相关。更多还原

【Abstract】 It is proved that aspirin can effectually prenvent the happening of myocardial infarction, cerebral apoplexy and other death of circulating system in many clinical trails. It is now used for the first-level and second-level prevention for thromboembolic disease. However, some patients still suffer from thromboembolic disease after regularly taking of aspirin because the existence of aspirin resistance. Our objective is to find out the prevalence and risk factors of aspirin resistance, and to investigate the correlationship between aspirin resistance and P-selection in platelet.Methods 50 patients with coronary disease(male 26, female 24) intook aspirin 100mg/d for two weeks. Platelet aggregation (PAG) induced with adenosine diphosphate (ADP) were detected. According to PAG, CHD patients was divided into two subgroups: aspirin-resistant subgroup and aspirin-sensitive subgroup. P-selection expression was detected before and after treatment.Results 9 patients(18%) showed AR.The prevalence was similar in male and famale(P=0.385). The blood LDL-C level(3.65±1.17 vs 2.93±1.03mmol/L, P=0.018), hypertension(66.7% vs 29.2%, P=0.03), total cholesterol level (5.43±1.6 vs 5.09±1.63mmol/L, P=0.042)and hemoglobin level(130±7.9 vs 139±14.75g/L, P=0.05)was higher in AR, compared with Aspirin sensitive patients. Logistic regression revealed that blood LDL-C level (or=3.26) and hypertension (or=3.89) were the independent factors of AR (P<0.05). The expression of P-selection was significantly higher in AR patients than in AS (2.97±1.64 vs 2.48±1.01, P=0.003). P-selection has no significant change in AR or AS groups before aspirin interference while they showed difference after interference respectively(2.97±1.64vs2.48±1.01, P=0.003). Group comparison revealed that P-selection level had no much difference before and after interference in AR subgroup(3.36±1.55 vs 2.97±1.64, P=0.08), compared with its significant deviation in AS subgroup(3.34±1.10 vs 2.48±1.01, P=0.03). Positive correlation was shown between PS and PAG in AR subgroup.Conclusion The incidence rate of AR is 18% and there is no significant difference between male and female. The blood LDL-C level and hypertension are the independent factors of AR. The trail also reveals that AR has no relationship with the age, weight, blood glouse, platelet, leukocyte and hemoglobin. P-selection expression can be used as an effective standard of measuring AR. Aspirin reduces the activation and aggregation of platelets and inhibit the expression of P-selection indirectly by irreversibly acetylating cyclooxygenase-1 (COX-1),and thereby reduces TXA2 produced by platelets. Positive correlation exists between PS expression and AR.更多还原