Pharmacokinetics of two modified release system of dipyridamole in beagle dogs

A novel floating osmotic pump controlled release system （FOP） and traditional matrix sustained release tablets （MT） of dipyridamole （DIP） were characterized in terms of pharmacokinetics, drug release, and in vitro-in vivo correlation. In vivo study was performed by a three-crossover study in six beagle dogs relative to the conventional tablet （CT）. A HPLC method for the determination of DIP in the plasma was developed. Cumulative percent of absorption fraction was compared to that of in vitro cumulative release. Both FOP and MT displayed obvious extended release characteristic in vivo while FOP showed a better extended release behavior. The bioavailability of FOP was higher than that of MT and a zero-order release linear correlation of DIP between fraction absorbed in vivo and fraction dissolved in vitro was established for FOP while not for MT. The results indicated the existence of an absorption window in upper part of the GI track of DIP, which meant that floating system could be excellent for the drug delivery. In addition, the in vitro model was a good choice for depicting in vivo absorption and for optimization of the formulation of FOP if it is needed to be bio-equivalent to MT.

Dipyridamole enhances inhibitory effect of adenosine on neutrophils in human peripheral blood

Objective： It was known that neutrophils play an important role in ischemic-reperfusion injury. In this study we tested the effect and its mechanism of dipyfidamole on neutrophils. Methods：Hydrogen peroxide（H2O2） production by neutrophils was determined using luminol amplified chemiluminescence and the percentage of activity was calculated by observing the uninhibited peak height. Results： Dipyfidamole per se produced a concentration-dependent inhibition of H2O2 by formyl-MetleuPhe（fMLP）-stimulated neutrophils. Dipyridamole at a low concentration（0.3 μ mol · L^-1） that per se affected neutrophils only slightly, enhanced markedly the effects of adenosine on neutrophils. On the other hand, dipyfidamole did not alter the inhibitory effect of NECA（5＇ -N-ethylcarboxamidoadenosine） on neutrophils. However, propentofylline, a known inhibitor of adenosine uptake, also gotten the same result. Conclusion：Dipyfidamole inhibited the production of H2O2 by fMLP-sfimulated neutrophils. Dipyfidamole at a low concentration enhanced the inhibitory effect of adenosine on neutrophils. The mechanism involved is probably due to the effect of dipyfidamole on adenosine uptake.

INDEPENDENT AND SYNERGIC INHIBITION OF DIPYRIDAMOLE AND RADIATION ON K562-AND K562/ADM CELL LINES IN VITRO

It is first demonstrated that dipyridamole (DP) and radiation were capable of significantly inhibiting, independently and synerglcally, clonogenlc growth in the two kinds of K562 cell lines, adriamycin (ADM) -sensitive and ADM- resistant. DP or radiation alone Increased clonogenlc Inhibition rate (CIR) in the two kinds of cell lines in a dose- dependent fashion. DP potentiated radiosensitivity and radiation increased inhibition of DP in the two kinds of cell lines. K562/ ADM cell lines were higher sensitive to DP. radiation and combination of them than K562 cell lines (P<0. 01). There was stronger synergic inhibition of clonogenlc growth in the two kinds of cell lines when pretreated with DP than when posttreated with DP (P<0. 01).

Clinical value of dipyridamole brain perfusion imaging in the diagnosis of ischemic cerebrovascular disease

Using dipyridamole stress test to evaluate cerebral blood flow reserve in cerebrovascular disease (CVD). Dipyridamole stress tests were performed first, the baseline SPECT images were obtained under similar conditions 2-5 days later. By visual and semiquantitative analysis, the responses of cerebral blood flow to dipyridamole were divided into the following four patterns: A: The dipyridamole SPECT showed an expanded area of hypoperfusion, Asymmetry Index(AI) and Uptake Rate(UR) were all decreased; B: Rest images was normal but new hypoperfused areas appeared on stress test with decreased Al and UR; C: Hypoperfused areas were decreased in size or disappeared after stress test with increased Al and UR; D: No changes showed in cerebral perfusion imaging patterns, and in Al and UR between stress and rest studies. Dipyridarnole brain perfusion imaging may be helpful to the diagnosis of CVD, to the decision the therapeutic plan, and to predicting the therapeutic effect.

Aspirin interruption before neurosurgical interventions:A controversial problem

Aspirin is widely used for primary or secondary prevention of ischemic events.At the same time,chronic aspirin consumption can affect blood clot formation during surgical intervention and increase intraoperative blood loss.This is especially important for high-risk surgery,including neurosurgery.Current European Society of Cardiology guidelines recommend aspirin interruption for at least 7 d before neurosurgical intervention,but this suggestion is not supported by clinical evidence.This narrative review presents evidence that challenges the necessity for aspirin interruption in neurosurgical patients,describes options for aspirin effect monitoring and the clinical implication of these methods,and summarizes current clinical data on bleeding risk associated with chronic aspirin therapy in neurosurgical patients,including brain tumor surgery,cerebrovascular procedures,and spinal surgery.

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity

BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.Platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases.Aspirin is the most classic antiplatelet agent.However,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.AIM To explore the impact of the antiplatelet effect of aspirin on the development of HCC.METHODS Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was established.CCK-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of HCC.RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways.Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC cells.Activated PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling axis.Additionally,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.CONCLUSION PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet activity.These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction

BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and mortality.Timely or improper treatment greatly affects patient prognosis.AIM To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life(QOL),anxiety and depression in CI patients.METHODS We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group(OG)(combination therapy of aspirin and edaravone,65 patients)or a control group(CG)(aspirin monotherapy,59 patients).The therapeutic effects,pre-and posttreatment National Institutes of Health Stroke Scale(NIHSS)scores,activities of daily living,degree of cognitive impairment,protein levels of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE)and S-100B,occurrence of adverse reactions,and serum high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere evaluated,detected and compared between the two groups.Finally,posttreatment QOL,anxiety,and depression were assessed by the Medical Outcomes Study 36-Item Short Form Health Survey Scale,Self-rating Depression Scale(SDS),and Self-rating Anxiety Scale(SAS),respectively.RESULTS Compared with the CG,the OG had markedly better therapeutic effects,greater improvements in activities of daily living,and better alleviation in cognitive dysfunction after treatment,as well as lower posttreatment NIHSS scores and serum NSE,GFAP,S-100B,hs-CRP,IL-6,and TNF-αlevels;the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL;and the OG also had lower SDS and SAS scores than the CG after treatment.CONCLUSION Aspirin plus edaravone had a good curative effect on CI.It can reverse cranial nerve damage in patients,improve neurological function and prognosis,and alleviate inflammation,anxiety,and depression;thus,it is considered safe and worthy of clinical application.

Application of aspirin and low molecular weight heparin in major orthopedic surgery:Meta analysis of a randomized controlled trial

Objective:The perioperative period of major orthopedic surgery is associated with a high risk of thrombosis,but the best chemopreventive agent for thrombosis prophylaxis is still inconclusive.For this reason,this paper evaluated the efficacy and safety of aspirin versus low-molecular heparin using a Meta-analysis.Methods:Ten randomized controlled studies on the application of aspirin and low-molecular heparin for the prevention of deep vein thrombosis in orthopedic major surgery were retrieved by computer searches of PubMed,CochraneLibrary,WebofScience,China Knowledge Network,Wanfang,and Vipul databases according to inclusion and exclusion criteria,and the literature was managed using Endnote software,and the data were analyzed using Revman 5.3 software was used to perform Meta-analysis of the extracted data,focusing on the effects of these two drugs on pulmonary embolism,deep vein thrombosis,major bleeding events,minor bleeding events,wound complications,mortality and blood loss within 90 days after major orthopedic surgery.Results:(1)Ten randomized controlled trials of high quality were included,with a total of 12,974 patients,7,026 in the aspirin group and 5,948 in the low-molecular heparin group;(2)Meta-analysis showed that aspirin had a higher incidence of pulmonary embolism(OR=1.59,95%CI:1.02 to 2.49,P=0.04)and deep vein thrombosis(OR=1.60,95%CI:1.26 to 2.02,P=0.0001)than low molecular heparin;(3)The incidence of major bleeding events(OR=0.85,95%CI:0.47 to 1.55,P=0.60),minor bleeding events(OR=0.79,95%CI:0.55 to 1.12,P=0.18),adverse wound reactions(OR=0.79,95%CI:0.48 to 1.31,P=0.36),mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)in both drug groups,mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)were not statistically significant.Conclusion:Low-molecular heparin was superior to aspirin in the prevention of pulmonary embolism and lower extremity deep vein thrombosis after major orthopedic surgery,but the safety and adverse drug reactions of both groups were basically similar.Based on this,the authors recommend that low-molecular heparin should be preferred for the prevention of deep vein thrombosis in major orthopaedic surgery;however,the inclusion of randomized controlled trials remains limited,necessitating high-quality,large-sample,long-term follow-up clinical studies.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

Balancing bleeding,thrombosis and myocardial injury:A call for balance and precision medicine for aspirin in neurosurgery

Perioperative management of antiplatelet therapy involves a delicate balancing of the risk of periprocedural blood loss with the cardiovascular and thrombotic risk to the patient.Due to the unique nature of neurosurgery,perioperative bleeding may have devastating consequences and cause major morbidity and mortality.The recommendation to discontinue aspirin prior to major neurosurgical procedures rests upon conventional practice,expert consensus with priority given to avoidance of any major bleed.On the contrary recent prospective data do not support the existence of additional bleeding risk in patients continuing aspirin compared to those who stop aspirin prior to procedure.Patients with cardiova-scular and metabolic comorbidities are increasingly encountered in the operation theatre these days.In these patients,prevention of myocardial injury after non-cardiac surgery(MINS)is an important focus for perioperative risk reduction.Prolonged(≥7 days)cessation of antiplatelets is one of the most important predictors of MINS.This complicated milieu of risks and benefits highlights the difficulty of practicing evidence-based medicine and minimizing harm in patients on aspirin needing neurosurgery.

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)metformin.During a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related mortality.Statin,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Analysis of the Therapeutic Effect of Clopidogrel Bisulfate Tablets + Aspirin Enteric-Coated Tablets on Acute Myocardial Infarction

Objective:To investigate and analyze the clinical effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on acute myocardial infarction(AMI)patients.Methods:The study period was from January 2020 to December 2023,the sample source was 82 AMI patients admitted to our hospital,grouped into an observation group(n=41)and a control group(n=41)by the numerical table method.The patients in the control group were treated with aspirin enteric-coated tablets,and the patients in the observation group were treated with aspirin enteric-coated tablets combined with clopidogrel bisulfate.The clinical efficacy,coagulation indexes,and the incidence of cardiovascular adverse events between the two groups were compared.Results:The clinical efficacy of the observation group was higher than that of the control group(P<0.05);the platelet aggregation rate(PAR)of the observation group was lower than that of the con-trol group after treatment(P<0.05),and there was no significant difference in the prothrombin time(PT)and activated partial thromboplastin time(APTT)between the two groups(P>0.05).The incidence of cardiovascular adverse events in the observation group was lower than that of the control group(P<0.05).Conclusion:The treatment effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on AMI patients is remarkable.It reduces the PAR and the incidence of cardiovascular adverse events,so this treatment method should be popularized.

Analysis of the Effectiveness of Clopidogrel Combined with Aspirin in the Treatment of Coronary Heart Disease in Community-Dwelling Elderly

Objective:To analyze the combined therapeutic effect of clopidogrel(CLO)and aspirin(ASP)on coronary heart disease(CHD)in community-dwelling elderly.Methods:Thirty elderly patients with CHD who were admitted to the Xinxin Community Health Service Station,Pangzhuang Street,Quanshan District,Xuzhou City,from November 2020 to November 2022 were selected and randomly grouped into an observation group and a control group,with 15 cases in each group.The observation group was given the combination of CLO and ASP and the reference group was given only ASP.The total effective rate and other treatment indicators between the two groups were compared.Results:The total effective rate of the observation group(93.33%)was higher than that of the reference group(60.00%)(P<0.05).The adverse drug reaction rate(13.33%)and long-term cardiovascular adverse event rate(6.67%)of the observation group were lower than those of the reference group at 46.67%and 40.00%respectively,(P<0.05).Before treatment,the two groups had no difference in the quality-of-life scores(P>0.05).After treatment,the quality-of-life scores of the observation group were higher than those of the reference group(P<0.05).Conclusion:CLO combined with ASP improved the therapeutic effect of community-dwelling elderly patients with CHD,reduced adverse reactions during medication,prevented adverse cardiovascular events,and comprehensively improved the patient’s quality of life.

阿司匹林抵抗和脂蛋白相关磷脂酶A2与复发性缺血性脑卒中的相关性分析

目的探讨非心源性卒中患者阿司匹林抵抗和脂蛋白相关磷脂酶A2(Lp-PLA2)与缺血性脑卒中复发的相关性。方法选取2021-10—2022-10在永城市人民医院住院的发病7 d内的急性非心源性缺血性脑卒中患者72例,基于临床病史和神经影像学证据分为初发组(n=36)和复发组(n=36),入院后规律服用阿司匹林7 d。采用血栓弹力图测定阿司匹林抵抗,并测定血清Lp-PLA2水平。比较初发组和复发组阿司匹林抵抗、Lp-PLA2水平,分析阿司匹林抵抗、Lp-PLA2与缺血性脑卒中复发之间的相关性。采用多元Logistic回归分析筛选复发性卒中独立危险因素,ROC曲线下面积评价相关危险因素的预测价值。结果36.1%的复发性卒中患者存在阿司匹林抵抗,19.4%的初发患者存在阿司匹林抵抗,2组比较差异有统计学意义(P<0.001)。复发性卒中患者血清PLA2水平中位数160.0μg/L,初次发病患者为125.0μg/L,2组比较差异有统计学意义(P=0.008)。多元Logistic回归分析显示阿司匹林抵抗和高PLA2水平是复发性缺血性脑卒中的影响因素,阿司匹林抵抗患者卒中复发风险增加4.06倍(P=0.042),高于Lp-PLA2中位值患者的4.37倍(P=0.011)。阿司匹林抵抗和Lp-PLA2预测卒中复发的ROC曲线下面积分别为0.753(95%CI:0.641~0.873)和0.683(95%CI:0.559~0.807)。结论与初发卒中患者相比,复发性卒中患者阿司匹林抵抗的比率和血清Lp-PLA2水平均明显升高,可作为复发性卒中的预测因素。

补肾活血方对抗磷脂抗体阳性反复种植失败患者妊娠结局的影响

目的:观察补肾活血方对抗磷脂抗体阳性反复种植失败(RIF)患者妊娠结局的影响。方法:选取188例抗磷脂抗体阳性RIF患者,按随机数字表法分为补肾活血方组和对照组,两组各94例。两组均给予冻融胚胎移植方案治疗,对照组同时口服拜阿司匹林治疗,治疗组在对照组基础上给予补肾活血方治疗。比较两组子宫内膜容受性超声检测指标、子宫内膜容受性分子标志物指标、中医证候积分及临床疗效、安全性。结果:两组基线时子宫内膜厚度及血流参数比较,无统计学差异(P>0.05)。两组胚胎移植前1天子宫内膜厚度及子宫内膜收缩期峰值速度/舒张末期流速(S/D)较基线时升高,子宫内膜搏动指数(PI)、阻力指数(RI)较基线时下降(P<0.05)。治疗组胚胎移植前1天子宫内膜厚度及子宫内膜S/D高于对照组,子宫内膜PI、RI低于对照组(P<0.05)。治疗组种植窗期整合素β3低于对照组,整合素β1、同源框基因11(HoxA11)高于对照组(P<0.05)。两组治疗后中医证候积分较治疗前降低,治疗组更低(P<0.05)。治疗组临床妊娠率62.22%、活产率55.56%高于对照组,胚胎种植率40.27%,流产率10.71%,与对照组比较,无统计学差异(P>0.05)。结论:补肾活血方可改善抗磷脂抗体阳性RIF患者子宫内膜容受性,提高临床妊娠率,降低早期流产率。

新型无机/有机复合发光材料Eu(aspirin)_3phen-MCM-41的光学性能

在室温下,将MCM-41和热处理后的发光客体Eu(aspirin)3phen进行组装,通过XRD、N2-吸脱附和PL等表征技术对组装体进行了研究,考察其光致发光性能。结果表明:Eu(aspirin)3phen进入MCM-41孔道后,充当了'二次模板剂',使MCM-41的骨架有序性增加。经热处理后Eu(aspirin)3phen与MCM-41组装后,组装体的发光强度与相应Eu(aspi-rin)3phen粉末相当。未焙烧的MCM-41表面和稀土有机配合物成键后,Eu(aspirin)3phen分子出现反演中心,5D0→7F2跃迁明显减弱,而焙烧后MCM-41表面对Eu3+的5D0→7F2电偶极跃迁强度没有影响。

Simultaneous Determination of Tetramethylpyrazine and Aspirin in a New Compound Formulation by Liquid Chromatography

Aim To establish a reversed-phase liquid chromatographic (LC) method forsimultaneous determination of tetramethylpyrazine (TMP) and aspirin in a new compound formulation.Methods Chromatographic separation of the two drugs was achieved on a Diamonsil C_(18) column, usinga binary mixture of methanol-1.5% acetic acid (35:65, V/V, pH = 3.1) as mobile phase at a flow rateof 1.0 mL·min^(-1). Results Separation was completed in less than 12 min. Benzoic acid was used asthe internal standard. Recoveries at levels corresponding to 80 % to 120 % of the label claim ofthe formulation ranged from 99.6 to 100.3 % for aspirin and from 99.9 to 101.3% for TMP. The linearrange was 12.6 - 150.9 μg·mL^(-1)(r= 0.9997, n = 5) for aspirin and 25.0- 300.0 μg·mL^(-1) (r =0.9999, n = 5) for TMP. Conclusion The method developed can be used for the simultaneousdetermination of TMP and aspirin in pharmaceutical preparations.

VerifyNow-Aspirin评估阿司匹林抗血小板效应及其影响因素分析

目的联合VerifyNow-Aspirin与尿11-脱氢-血栓烷B2测定,评估阿司匹林抗血小板效应及其影响因素。方法选择规律服用阿司匹林至少两周的冠心病患者264例,年龄33～86(65.31±10.23)岁,其中男147例(55.7%),女117例(44.3%)。阿司匹林标准剂量组(100mg/d)241例,低剂量组(25～75mg/d)23例。采用VerifyNow-aspirin系统测定服用阿司匹林后血小板残余活性(用ARU表示),酶联免疫吸附法检测尿11-脱氢-血栓烷B2(11-DH-TXB2)浓度,并记录入选人群的基线资料及心血管疾病危险因素。结果以ARU≥550为切割值定义阿司匹林低反应性(ALR)人群,标准剂量组人群中ALR发生率为8.6%(23例)。ALR人群尿11-DH-TXB2显著高于正常反应组,差异有统计学意义(2.85±0.73pg/ml vs 2.51±0.49pg/ml,P<0.05),但二者之间相关性较差(r=0.18,P=0.04)。女性、高血压及糖尿病均为ARU升高的预测因素(均P<0.05),但其组间尿11-DH-TXB2水平差异无统计学意义(均P>0.05)。与阿司匹林标准剂量组比较,低剂量组人群残余血小板活性显著增强,同时伴有尿11-DH-TXB2升高(均P<0.05)。结论阿司匹林抗血小板效应存在个体差异,且具有一定量效关系,而VerifyNow和尿11-DH-TXB2对评估阿司匹林抗血小板效应及其发生机制具有一定互补性。

小剂量Aspirin对动脉粥样硬化兔主动脉斑块炎症反应和COX-2表达的影响

目的探讨小剂量阿司匹林对兔动脉粥样硬化主动脉斑块炎性过程和COX-2表达的影响。方法24只雄性新西兰兔随机分为对照组(喂食普通兔料)、高脂模型组(喂食高脂饲料)、阿司匹林组(喂食高脂饲料并给与小剂量阿司匹林干预),饲养12周后处死动物,取主动脉进行病理学检查,测定斑块面积,采用免疫组化方法观察各组巨噬细胞的表达情况,Western-bolt分析COX-2的表达。结果病理学大体观察发现,对照组、高脂模型组和阿司匹林组主动脉壁脂质斑块面积占整条主动脉内壁面积的百分比分别为0%、(59.62±10.74)%、(48.33±7.85)%,各组间两两比较均有显著性差异(P<0.05)。阿司匹林组斑块区巨噬细胞含量、COX-2表达明显低于高脂模型组。结论小剂量阿司匹林干预可以通过抑制病灶区的炎症反应、COX-2的表达来有效减轻高脂饮食所致的新西兰兔动脉粥样硬化的严重程度。