Effect of polymorphism and type Ⅱ diabetes on aspirin resistance in patients with unstable coronary artery disease

Background Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease.Methods Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1 Bα (C1018T), PI(A1/A2), P2Y1(A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness.Results A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P ＜0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r=0.038, P=0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR.Conclusions In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-g24T allele was involved in AR. Diabetes was an independent risk factor of AR.     

CORRELATION BETWEEN THE POLYMORPHISM OF GLYCOPROTEINⅠa GENE AND ACUTE CORONARY SYNDROME

Objective The platelet membrane glycoprotein (GP)Ⅰa/Ⅱa plays a major part as a primary collagen receptor in platelet function. Previous studies indicated that variations of GPⅠa/Ⅱa density and function are associated with the 807 C/T polymorphism of GPⅠagene in American and Spanish Caucasian populations. This study investigated the correlation between acute coronary syndrome (ACS) and 807 C/T dimorphism of GPⅠa gene in Chinese of Han ethnicity. Methods A case-control study was carried out, including 75 patients with either acute myocardial infarction (AMI) or unstable angina pectoris (UAP), and 65 controls with no history of coronary heart disease, thrombogenic and hemorrhagenic diseases. Genotypes of GPⅠa were checked by polymerase chain reaction-sequence specific primers (PCR-SSP) technique. Results The frequencies of both homozygotes and heterozygotes for T807 allele (TT TC) were significantly higher in patients with AMI than in controls (62.16% vs 33.85%, P＜0.01; odds ratio 3.21).The prevalence of (TT TC) genotypes was also markedly higher in patients with UAP than in controls (65.79% vs 33.85%, P ＜ 0.005; odds ratio 3.76). There was significant difference in the distribution of (TT TC) genotypes not only between all patients and controls (64.00% vs 33.85%, P ＜0.005; odds ratio 3.47) but also between the two subgroups aged ＜ 60 years (70.00% vs 38.24%, P ＜0.005; odds ratio 3.77). However, there was no significant difference in the distribution of (TT TC) genotypes between patients with AMI and with UAP. Platelet GPⅠa T807 allele remained significantly associated with AMI and UAP by multiple logistic regression (odds ratio 4.94). Conclusion This study suggests a strong association between presence of GPⅠa T807 allele and ACS. T807 allele can be a marker of genetic susceptibility to ACS.     

Effect of polymorphism and type II diabetes on aspirin resistance in patients with unstable coronary artery disease

Background  Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease.

Methods  Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1Bα (C1018T), Pl (A1/A2), P2Y1(A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness.

Results  A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P <0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r=0.038, P=0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR.

Conclusions  In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-924T allele was involved in AR. Diabetes was an independent risk factor of AR.

     

Effect of Xiaoyu Zhixue Tablet (消瘀止血片) on Expression of Platelet Membrane Glycoproteins in Patients with Hemorrhagic Thrombopathy

Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Methods: The total of 148 patients with hemorrhagic thrornbopathy were randomly divided into two groups, the traditional Chinese medicicne (TCM) group (n=98) treated with XYZXT and the Western medicine (WM) group (n = 50) treated with adrenosin, vitamins C, K and P, both for 6 months.The therapeutic effect and the recovery rate of platelet aggregation in the two groups were observed. And platelet membrane glycoprotein (GP) Ⅰ b/Ⅸ, GP Ⅱ b/Ⅲ a complexes, GP Ⅰ b, GP Ⅱ b, GPⅢ a and P-selectin were analyzed by flow cytometry in both groups before and after treatment and also in 34 normal healthy subjects. Results: The total effective rate of hemostasis was 89.8% in TCM group and 54.0% in the WM group (X2 =45.83, P＜0.01), and the recovery rate of platelet aggregation was 72.4% and 4.0% respectively (X2 = 62.06, P＜0.01). The fluorescence intensity of GP Ⅰ b/Ⅸ, GP Ⅱ b/Ⅲ a complexes, GP Ⅰ b, GP Ⅲ a and P-selectin were lower in both groups before treatment than those in the healthy subjects. Expression of above-mentioned marks was elevated in TCM group after 6 months' therapy, which was insignificantly different as compared with the healthy subjects (P＞0.05) and higher than those in the WM group (P＜0.05).Conclusion: One of the mechanisms in treating hemorrhagic thrombopathy with XYZXT is that it could regulate the expression of GP Ⅰ b/Ⅸ, GP Ⅱ b/Ⅲ a complexes, GP Ⅰ b, GPⅢ a and P-selectin at the level of receptor protein.     

Effects of glycoprotein Ⅱb/Ⅲa antagonists and chloride channel blockers on platelet cytoplasmic free calcium

Platelet activation plays an important role in thrombosis. Platelet glycoprotein Ⅱ b/Ⅲ a （ GPⅡ b/Ⅲ a ） is the receptor of fibrinogen. Platelet cross-linking with fibrinogen through GP Ⅱ b/Ⅲ a is the process of thrombosis. Ca^2＋ is an important intracellular second messenger in platelet activation. It has been reported that GP Ⅱ b/Ⅲ a receptors were involved in the calcium influx of activated platelet, and GP Ⅱ b/Ⅲ a receptor had characteristics of calcium channel or an adjacent calcium channel.     

Earlier application of loading doses of aspirin and clopidogrel decreases rate of recurrent cardiovascular ischemic events for patients undergoing percutaneous coronary intervention

Background  Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention. Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation.

Methods  Thrombelastograph (TEG) determinations were used to evaluate the effect of antiplatelet therapy. According to the results, 90 patients were divided into three groups and given different doses of aspirin and clopidogrel. Thirty patients with both an inhibition rate of aspirin >50% and an inhibition rate of clopidogrel >50% were defined as the control group. Sixty patients with an inhibition rate for aspirin <50% and an inhibition rate for clopidogrel <50% were defined as the resistance group. Patients in resistance group were randomly assigned to be given a routine dose (100 mg aspirin plus 75 mg clopidogrel per day, which we called a resistance plus routine dose group, R+R) and a loading dose (200 mg aspirin and 150 mg clopidogrel per day, which we called resistance plus loading dose group, R+L) of antiplatelet therapy. A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events.

Results  After 6 months of antiplatelet therapy, the inhibition rate of aspirin in the R+L group increased from (31.4±3.7)% to (68.6±7.1)%, which was significantly higher than that in R+R group, (51.9±8.2)% (P <0.01). The inhibition rate of clopidogrel in the R+L group increased from (22.1±3.8)% to (60.2±7.4)%, which was significantly higher than in the R+R group, (45.9±4.3)% (P <0.01). The occurrence rates of cardiovascular ischemic events, stent thrombosis, recurrent unstable angina and myocardial infarction in the R+R group were 20%, 36% and 17%, respectively. Occurrence was significantly increased compared with that in the control group, 3%, 10% and 1%, respectively (P <0.01). In contrast, the occurrence rates in the R+L group (10%, 23% and 6%, respectively) were attenuated compared with those in the R+R group (P <0.01), although still higher than in the control group (P <0.01).

Conclusions  Almost all of the cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention. According to the result of TEG determinations, earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events.

     

Expression of Platelet Membrane Glycoprotein Ib/Ⅸ/Ⅴ Complex,a Receptor of Thrombin,in Patients with Hemorrhagic Thrombopathy

To investigate the role of platelet membrane glycoprotein (GP) Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy (HT), the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity (MFI), were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant (P<0.05). There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects (P>0.05). It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.     

Effect of Xiaoyu Zhixue Tablet (消瘀止血片) on the expression of platelet membrane glycoprotein I b/IX/V complex in patients with chronic renal failure

ABSTRACT Objective： To investigate the effect of Xiaoyu Zhixue Tablet （消瘀止血片, XYZXT） on the expression of platelet membrane glycoprotein （GP） Ⅰ b/Ⅸ/Ⅴ complex and GP Ⅰ b α in patients with chronic renal failure （CRF） in early metaphase. Methods： Fifty-one patients with CRF in early metaphase （treated group） were treated with XYZXT, 3 months as the course of treatment for 2 courses. The previous therapies remained unchanged. Flow cytometry was used to assess the expression of platelet GP Ⅰb/Ⅸ/Ⅴ complex and GP Ⅰb α in patients with CRF, and turbidity method was used to determine the platelet maximum aggregation rate （MAR）, meanwhile the renal function was measured. The final data were compared with those before the treatment, and with those in the normal control group （31 healthy subjects）. Results： Compared with the normal control group, expressions of GP Ⅰ b/Ⅸ/Ⅴ complex and GPⅠb α, and platelet MAR in CRF patients were significantly lower （P=0.007,P=0.001,P=0.009） before the treatment; after the treatment with XYZXT, the above indexes in CRF patients were remarkably increased （P=0.033,P=0.026, P=0.045）, but still lower than those in the normal control group, however, it was not statistically significant. Conclusion： （1） The expression of GP Ⅰ b/Ⅸ/Ⅴ complex in CRF patients of early metaphase was decreased, which lead to platelet aggregation dysfunction. This might be one of the reasons for the hemorrhagic trend in CRF. （2） XYZXT was able to upgrade expressions of GP Ⅰb/Ⅸ/Ⅴ complex and GPⅠb α in CRF patients, improve platelet function and clown-regulate platelet activation in patients with CRF.     

Expression of Platelet Membrane Glycoprotein Ib/Ⅸ/Ⅴ Complex,a Receptor of Thrombin,in Patients with Hemorrhagic Thrombopathy

To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.     

The Association between Polymorphism of TNF-α Gene and Hypertensive Disorder Complicating Pregnancy

To study whether the development of hypertensive disorder complicating pregnancy is associated with -308G→A, -850C→T mutation at promoter of TNF-α gene, the -308G→A, -850C→T polymorphism was examined in patients and healthy pregnant women by PCR-RFLP technique. The frequencies of genotype and allele were compared between the two groups. The re- sults showed that with -308G→A polymorphism distribution, the allele frequency of TNF2 and the frequency of the genotype TNF2/1 in the patient group was significantly higher in the patient group than in control group (P<0.05). A significant difference in genotype distribution of -850C→T poly- morphism was observed between the two groups. The allele frequencies of T in patient group was higher in the control group as compared with the patient group. The frequencies of CT and TT genotypes were lower in the patient group. It is concluded that the TNF2 allele of -308 is associated with the occurrence of hypertensive disorder complicating pregnancy, while T allele of -850 may be the protective factor against the development of the disease. TNF2/1 CC may be susceptibility genotype of hypertensive disorder complicating pregnancy.     

Association of the platelet membrane glycoprotein I a C807T gene polymorphism with aspirin resistance

Summary To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein I a (GP I a) gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin (100 mg/d) for 7 days. Platelet aggregation function was detected using adenosine diphosphate (ADP) and arachidonic acid (AA) before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function: an aspirin resistant (AR) group, an aspirin semi-responder (ASR) group and an aspirin-sensitive (AS) group. Platelet GP I a gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers (PCR-SSP). The results showed that T allelic frequency in AR group and ASR group were higher that of AS group (P<0.005), and the prevalence of genotypes (TT+TC) of these two groups was significantly higher than that in AS group (P<0.05). Platelet GP I a T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression (OR=3.76, 95% CI: 2.87–9.58). The results suggest that inherited platelet GP I a variations may have an important impact on aspirin resistance and the presence of GP I a T allele may be a marker of genetic susceptibility to aspirin resistance.     

Association of the Platelet Membrane Glycoprotein Ⅰa C807T Gene Polymorphism with Aspirin Resistance

To explore the correlation between the C807T polymorphism of platelet membrane gly- coprotein Ⅰa (GPⅠa) gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin (100 mg/d) for 7 days. Platelet aggregation function was detected using adenosine diphosphate (ADP) and arachidonic acid (AA) before and after the administration of aspi- fin. Then the subjects were divided into three groups according to the results of platelet aggregation function: an aspirin resistant (AR) group, an aspirin semi-responder (ASR) group and an aspi- fin-sensitive (AS) group. Platelet GPⅠa gene 807CT polymorphism was examined by means of po- lymerase chain reaction-sequence specific primers (PCR-SSP). The results showed that T allelic fre- quency in AR group and ASR group were higher that of AS group (P<0.005), and the prevalence of genotypes (TT+TC) of these two groups was significantly higher than that in AS group (P<0.05). Platelet GPⅠa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression (OR=3.76, 95% CI: 2.87-9.58). The results suggest that inherited platelet GPⅠa variations may have an important impact on aspirin resistance and the presence of GPⅠa T allele may be a marker of genetic susceptibility to aspirin resistance.     

脑梗死患者抗血小板药物抵抗的发生率及相关因素研究

目的 探讨脑梗死患者阿司匹林抵抗（AR）及氯吡格雷抵抗（CR）的发生率及其相关因素。方法 连续性收集2010年10月～ 2013年1月在北京大学人民医院神经内科住院的脑梗死患者154例,其中男性104例,女性50例;患者年龄36～95岁,平均年龄66.5±11.3岁.患者口服阿司匹林肠溶片或氯吡格雷片7天后采集外周静脉血,光学聚集法测定血小板聚集率.对于服用阿司匹林患者,10μmol/L二磷酸腺苷（ADP）诱导的血小板聚集率≥70％并且500μmol/L花生四烯酸（AA）诱导的血小板聚集率≥20％定义为阿司匹林抵抗,仅满足其中一项为阿司匹林半抵抗（ASR）.对于服用氯吡格雷患者,10μmol/L ADP诱导的血小板聚集率≥70％定义为氯吡格雷抵抗.根据检测结果将患者分为阿司匹林抵抗组（AR＋ ASR）、阿司匹林敏感组（AS）及氯吡格雷抵抗组（CR）、氯吡格雷敏感组（CS）.比较各组患者的临床资料（性别、年龄、高血压病史、2型糖尿病史、吸烟习惯）及检验指标（血小板计数、血脂、血糖、糖化血红蛋白）.结果 100例患者口服阿司匹林肠溶片,AR的发生率为3％,ASR发生率为41％,阿司匹林抵抗及半抵抗总发生率为44％;阿司匹林抵抗组（AR＋ ASR）年龄为67.9 ±9.9岁,大于阿司匹林敏感组（AS）（63.3±12.3岁）（P＜0.05）;54例患者口服氯吡格雷片,CR的发生率为22.2％;2型糖尿病患者CR发生率明显升高（P＜0.05）.结论 脑梗死患者存在一定比例的阿司匹林抵抗和氯吡格雷抵抗,高龄可能是阿司匹林抵抗发生的危险因素,2型糖尿病可能是氯吡格雷抵抗发生的危险因素。     

糖尿病对小剂量阿司匹林治疗的阿司匹林抵抗的影响及相关因素分析

目的 探讨糖尿病对小剂量阿司匹林治疗的阿司匹林抵抗(AR)的影响及相关因素分析.方法 选择328例病情稳定的心脑血管病患者或有心脑血管病危险因素者,按照是否合并2型糖尿病将其分为合并糖尿病组(101例)和非糖尿病组(227例).两组均给予阿司匹林100 mg/d口服,连服14 d后分别以花生四烯酸(AA)、二磷酸腺苷(ADP)作诱导剂检测两组血小板聚集率.以同时满足AA诱导的血小板聚集率≥20%及ADP诱导的血小板聚集率≥70%者为AR;仅满足一项者为阿司匹林半抵抗(ASR),均不满足者为阿司匹林敏感(AS).分析两组AR、ASR、AS发生情况及影响AR/ASR的危险因素.结果 (1)合并糖尿病组ASR、AR+ASR发生率分别为35.6%和42.6%,非糖尿病组分别为23.8%和27.8%,两组ASR及ASR+AR发生率间差异有统计学意义(P＜0.05).(2)合并糖尿病组和非糖尿病组AR+ASR患者除血糖水平[分别为(7.1±2.6)mmol/L和(4.8±0.6)mmol/L]间差异有统计学意义(P＜0.01)外,其他临床相关指标间差异均无统计学意义(P＞0.05).(3)合并糖尿病组AR+ASR患者女性(60.5%)、吸烟者比例(11.6%)及TG水平[(1.7±0.7)mmol/L]与合并糖尿病组AS患者[分别为41.4%、29.3%和(2.2±1.7)mmol/L]比较,差异均有统计学意义(P＜0.05).(4)女性是合并糖尿病患者发生AR/ASR的独立危险因素[β=-1.185,χ2=7.738,P=0.005,OR=0.306,95%CI为(0.133,0.705)].结论 服用小剂量阿司匹林的心脑血管疾病合并糖尿病患者ASR及AR+ASR发生率高于心脑血管疾病非糖尿病患者.性别可能是糖尿病患者发生AR/ASR的相关危险因素之一.     

阿司匹林抵抗与GPⅢa基因多态性的相关性研究

目的研究阿司匹林抵抗患者的临床特征及其与血小板糖蛋白GPⅢa Leu33Pro基因位点多态性的关系。方法收集规律服用阿司匹林预防失败的脑梗死患者60例及服用相同剂量阿司匹林的社区体检者24例,以对照组95%尿11-脱氢-血栓素B2（11-DH-TXB2）水平的上界为标准判定阿司匹林抵抗,将病例组分为阿司匹林抵抗组（AR）和阿司匹林敏感组（AS）。比较AR组和AS组的临床特征及血小板糖蛋白GPⅢaLeu33Pro基因位点多态性。结果根据尿11-DH-TXB2的水平,发现31例患者存在AR,AR的发生率为51.67%。两组间年龄、性别,既往脑梗死病史、高血压及糖尿病患病率、TC、TG、HDL、LDL、FBG、PLT、WBC、RBC及Hb水平差异均无统计学意义（均〉0.05）。AR组和AS组GPⅢa Leu33Pro基因型及等位基因的分布无差别。结论温州地区阿司匹林预防失败脑梗死人群中AR的发生率是51.67%,与AS组相比,未发现明显临床特征。GPⅢa Leu33Pro基因位点多态性可能与AR的发生无关。     

不同阿司匹林抵抗类型原发性高血压患者血小板聚集率与血栓素B_2的检测及其意义

目的探讨不同阿司匹林抵抗类型原发性高血压患者服用阿司匹林后血小板聚集率（PAG）及血、尿血栓素B2（TXB2）的变化及临床意义。方法将101例原发性高血压患者根据阿司匹林抵抗的不同分为阿司匹林抵抗（AR）组9例，阿司匹林半抵抗（ASR）组23例，阿司匹林敏感（AS）组69例。分别测定各组患者服用阿司匹林前及服用阿司匹林1周（服用剂量为100mg／d）后PAG及血、尿TXB2浓度，并进行对比分析。结果用药前3组问各检测指标的差异均无统计学意义（均P〉0．05），服用阿司匹林1周后，3组患者各检测指标均显著低于用药前（均P〈0．01）；与AS组用药后比较，ASR组各指标并无明显差异（均P〉0．05）。而AR组各检测指标均显著高于AS组（均P〈0．01）；与ASR组用药后比较，AS组各指标并无明显变化（均P〉0．05），AR组血TXB2及尿TXB2浓度均显著高于ASR组，但PAGAA及PAGADP并无明显变化（均P〉005）。此外，血浆TXB，浓度与PAGAD，呈现显著的正相关（P〈0．01），与PAGAA亦表现出明显的相关性（P〈0．05）；但尿TXBz浓度与PAGADP及PAGAA均未表现出明显的相关性（均P〉005）。结论阿司匹林可降低原发性高血压患者的PAG和TXB2，有可能在一定程度上降低原发性高血压患者血栓形成的危险；原发性高血压患者血TXB2浓度与AR有一定相关性，亦可作为类似于PAG的另一种生化检测指标，对指导临床治疗，尤其是指导制定AR患者用药方案提供了较为重要的参考。     

阿司匹林抵抗动物模型的制备及评价

目的:探索性建立阿司匹林抵抗(AR)的金黄地鼠动物模型,并进行评价。方法:选用健康雄性金黄地鼠130只,分为2组,造模组120只,普通饲料组10只。造模组采取高脂高糖高盐饲养12周,同时给予灌胃给药(0.74g/kg/d阿司匹林+2.22g/kg/d布洛芬)和吸烟4周,以建立阿司匹林抵抗(AR)模型。采用血小板聚集试验作为AR判定标准:腺苷二磷酸(ADP)诱导的血小板平均聚集率≥70%,花生四烯酸(AA)诱导的血小板平均聚集率≥20%,同时符合两项者为AR,符合其中一项者为阿司匹林半抵抗(ASR)。结果:多因素造模组,AR和ASR金黄地鼠的PAG均明显升高(P<0.01)。AR模型6只,发生率为5%;ASR模型28只,发生率为23%。结论:通过对AR产生的病理环境的模拟,多种危险因素的综合作用,实验成功制造出AR金黄地鼠动物模型。     

Effect of the platelet membrane GP Ⅰ a gene polymorphism in the pathogenesis of unstable angina pectoris

Objective: To investigate the effect of platelet membrane glycoprotein(GP) Ⅰ a gene polymorphism in the pathogenesis of unstable angina pectoris (UAP) in Chinese people. Methods: Collagen type Ⅰ -induced platelet aggregation was measured in 33healthy subjects in vitro. Plasma level of α-granule membrane protein (GMP-140) was measured in both the above 33 healthy subjects during fasting and 35 patients with recent onset effort anina during rest onset within 24 h after hospitalization. Furthermore, the platelet membrane GP Ⅰ a gene 807C/T polymorphism was checked in all subjects with polymerase chain reaction-sequence specific primers(PCR-SSP)technique. Results: The lag time before 30% platelet aggregation was significantly longer in healthy subjects with CC genotype than with TC genotype ( P ＜0.01). However, there was no significant difference in the maximal platelet aggregation between healthy subjects with the above two genotypes. Plasma level of GMP-140 was significantly higher in TC genotypic patients with recent onset effort angina than in CC genotypic patients with the same type of UAP( P ＜ 0.05) and healthy subjects ( P ＜ 0.01), furthermore, there was also significant difference between the latter two groups( P ＜ 0.05). Conclusion: The rapid initiation of collagen-induced platelet aggregation may be associated with platelet membrane GP Ⅰ a T807 allele, which may play an important role in the pathogenesis of UAP.     

急性冠脉综合征抗血小板治疗药物抵抗及与COX-1基因多态性的相关性

目的:研究急性冠脉综合征(ACS)患者对阿司匹林联合氯吡格雷双重抗血小板治疗的反应并探讨药物抵抗与血小板COX-1基因A842G位点的相关性。方法:154例ACS患者,以花生四烯酸(AA)作为诱导剂测定血小板聚集率(PAG)。ELISA法测定尿11-脱氢-血栓素B2(11-DH-TXB2)水平。分析血小板COX-1基因A842G位点的基因型。计算患者2周内主要临床心脏事件(MACE)发生率。结果:①154例ACS患者PAG及尿11-DH-TXB2水平均明显升高,且急性心肿梗死(AMI)患者高于不稳定性心绞痛(UAP)患者,组间比较存在统计学差异(t=2.994,P<0.01;t=2.053,P<0.01);②双重抗血小板药物抵抗(AR)6例,抵抗发生率为3.90%;③COX-1基因A842G位点基因型AA型150例(97.40%),AG型4例(2.60%)。AR患者6例,其中AA型患者5例(83.33%),AG型患者1例(16.67%),组间比较存在统计学差异(χ2=43.560,P<0.01);④2周内AR组MACE率33.33%(2例),AS组4.05%(6例),组间比较存在统计学差异(χ2=22.73,P<0.01)。结论:①ACS患者存在不同程度的血小板活化状态,且AMI患者高于UAP患者,高血小板活化状态能引起更为严重的急性心脏事件;②COX-1基因A842G位点单核苷酸多态性可能与AR的发生有关,含有G突变基因患者更易发生AR;③AR患者更易发生心脏临床事件。