阿司匹林在防治心脑血管疾病中的性别差异

循证医学研究证实，阿司匹林对心脑血管病的防治有肯定的价值。阿司匹林作为抗血小板聚集药物，降低缺血性血管事件的作用机制是抑制血小板中花生四烯酸环氧化酶1（COX1），减少血栓素A2（TXA2）生成，从而抑制血小板释放二磷酸腺苷（ADP）和血小板聚集的激活。由于血小板无细胞核，不能生成新的COX，所以阿司匹林的这种作用不可逆。小剂量阿司匹林不可逆地乙酰化COX而抑制TXA2形成，并不抑制内皮细胞前列腺素（PG）合成，故不会对血管舒张功能造成影响。目前，阿司匹林被广泛应用于缺血性血管疾病防治。     

替罗非班在动脉粥样硬化性脑血管疾病中的临床应用专家共识

<正>抗血小板治疗是血栓栓塞性疾病如急性冠脉综合征(acute coronary syndrome,ACS)和缺血性卒中的基本治疗策略。现有的抗血小板药物中(表1),阿司匹林通过抑制环氧合酶和血栓素A_2的合成发挥抗血小板聚集的作用,噻吩吡啶类(氯吡格雷、替格瑞洛)通     

单核苷酸多态性与阿司匹林抵抗的研究进展

在破裂的动脉粥样硬化斑块溃疡上，活化的血小板聚集导致血栓形成。阿司匹林是临床 最常用的抗血小板聚集药物之一，但是部分患者服用阿司匹林后不能有效地抑制血小板聚集，产生阿 司匹林抵抗现象，导致血栓事件再次发生。随着分子生物学技术的飞速发展及人类基因组计划的开展， 越来越多的研究证实，遗传因素在血栓事件中发挥着重要的作用。基因变异会对血小板功能产生影响， 导致血小板活性增加，影响阿司匹林治疗后的残存血小板聚集。现通过回顾国内外与单核苷酸多态性 导致阿司匹林抵抗有关的研究，进一步认识了阿司匹林抵抗的遗传因素。     

阿司匹林对脑梗死患者血清C反应蛋白影响及抗血小板聚集作用的临床观察

脑梗死(CI)有较高的发病率、致残率、病死率和复发率,目前公认口服阿司匹林(ASP)为预防缺血性脑卒中的可靠治疗.脑梗死的主要原因是动脉粥样硬化,近年来研究表明炎症在动脉粥样硬化的发生和发展中具有一定意义,C反应蛋白(CRP)为一种反映各种急慢性炎症的指标蛋白.血小板聚集功能增强,多见于高凝状态和血栓性疾病,高血压患者中血小板聚集功能较健康人群明显增强[1].阿司匹林的防治作用是由于其具有抗炎和抗血小板聚集作用.本文对口服阿司匹林75mg的91例脑梗死患者通过测定其血清CRP及血小板聚集率,观察阿司匹林的抗炎和抗血小板聚集作用.……     

阿司匹林在防治心脑血管疾病中的性别差异

循证医学研究证实,阿司匹林对心脑血管病的防治有肯定的价值.阿司匹林作为抗血小板聚集药物,降低缺血性血管事件的作用机制是抑制血小板中花生四烯酸环氧化酶1(COX1),减少血栓素A2(TXA2)生成,从而抑制血小板释放二磷酸腺苷(ADP)和血小板聚集的激活.     

Stroke：当阿司匹林治疗失败后……

正在临床上,我们经常碰到一些患者在服用阿司匹林治疗时还是发生了缺血性卒中或短暂性脑缺血发作(transient ischemic attack,TIA),这可能与阿司匹林抗血小板作用不佳有关。服用阿司匹林的患者发生缺血性卒中或TIA后,很多医师愿意更换抗血小板药物,但是并不清楚最佳抗血小板治疗方案是什么。     

血栓弹力图评价脑梗死患者阿司匹林、氯吡格雷及其联合应用抗血小板治疗的作用研究

目的探讨采用血栓弹力图测定血小板抑制率评价脑梗死患者口服阿司匹林、氯吡格雷单药及其合用双联抗血小板治疗的作用。方法 98例住院的急性脑梗死患者按口服抗血小板药物分为阿司匹林组(39例)、氯吡格雷组(37例)及氯吡格雷+阿司匹林组(22例)。在患者服药21 d时,采用血栓弹力图仪(TEG-5000)检测花生四烯酸(AA)途径和二磷酸腺苷(ADP)途径诱导的血小板抑制率值,并与正常对照组(52人)进行比较。结果阿司匹林组和阿司匹林+氯吡格雷组AA途径诱导的血小板抑制率均显著高于正常对照组及氯吡格雷组(均P 0. 05)。氯吡格雷组和阿司匹林+氯吡格雷组ADP途径诱导的抑制率均明显高于正常对照组(均P 0. 05)。结论血栓弹力图可用于评价临床抗血小板药物的效果。服用阿司匹林能起到很好的抗血小板作用,氯吡格雷的效果稍差;而阿司匹林联合氯吡格雷的抗血小板作用更强。     

阿司匹林抵抗与基因多态性的研究进展

阿司匹林作为一种有效的抗血小板聚集药物广泛应用于心脑血管疾病的防治,临床观察显示阿司匹林能减少约25％的心脑血管疾病复发。然而,并不是所有患者都能从阿司匹林治疗中获益,有研究显示0．4％～83．3％个体对阿司匹林的抗血小板作用不敏感,     

阿司匹林对缺血性脑血管病患者抗血小板聚集作用的临床观察

阿司匹林是抗血小板聚集药物，广泛应用在心脑血管疾病的治疗和预防。本研究对日服阿刮匹林75mg的68例缺血性脑血管病（ICVD）患者通过测定其血小板聚集率观察阿司匹林的抗血小板聚集作用。     

阿司匹林和氯吡格雷抗血小板抵抗机制及临床治疗研究进展

脑梗死的发病率和致死率极高,其病因主要是动脉粥样硬化性脑血栓形成,抗血小板治疗是动脉粥样硬化性脑梗死急性期及二级预防的重要环节。阿司匹林和氯吡格雷是目前在临床应用最为广泛的抗血小板药物,但是抗血小板聚集作用在不同个体间存在较大差异,部分人群对于抗血小板药物的反应性较低,称为抗血小板药物抵抗。文中阐述了导致阿司匹林和氯吡格雷抵抗的主要机制以及临床上针对此种现象所采取的治疗措施,旨在为脑梗死患者的个性化治疗提供参考。     

In vitro model to test the thrombogenicity of coronary stents

Thrombotic occlusion is a major complication limiting the application of stents in coronary arteries. In an in vitro model we investigated the thrombogenicity of different stent materials and several medical regimens to prevent thrombotic occlusion. Experiments were conducted in a closed system of silicon tubing with circulating citrated platelet rich plasma of healthy volunteers (n=7) and of patients (n=7 for each condition). Patients were either treated with phenprocoumon or with high or low dose heparin in combination with aspirin alone (100 mg) or aspirin (990 mg) plus dipyridamole (225 mg). After placement of tantalum wire stents into the system platelet aggregates were visible after 13.5 ± 3.0 min, and occlusion occurred after 15.0 ± 3.5 min. Similarly, with implanted stainless steel stents aggregation was seen after 13.0 ± 3.5 min and thrombosis occurred after 14.5 ± 3.5 min (p<0.001 vs control without stent). Microscopic examination revealed combined platelet fibrin thrombi occluding the lumen. Platelet components predominately covered stent wires, particularly at crossing points. In all experiments high-dose heparin prevented platelet aggregate formation and stent occlusion independently of additional aspirin or aspirin plus dipyridamole; perfusion time > 60 min (p<0.001 vs no heparin). Low-dose heparin could not prevent clotting. With aspirin alone aggregates were visible after 16.0 ± 4.0 min and clotting occurred after 23.0 ± 5.0 min. In combination with dipyridamole aggregates were visible after 15.5 ± 5.0 min and clotting after 21.0 ± 4.0 min (NS vs aspirin alone). Phenprocoumon prevented platelet aggregate formation and stent occlusion; perfusion time > 60 min. Thus, in our in vitro model both platelet aggregate formation and coagulation play an important role for stent occlusion. High-dose heparin and phenprocoumon prevented both. Low-dose heparin was less effective and could not prevent clotting even in combination with aspirin and dipyridamole.     

Effects of Gonadotrophin-Releasing Hormone Outside the Hypothalamic-Pituitary-Reproductive Axis

Gonadotrophin-releasing hormone (GnRH) is a hypothalamic decapeptide with an undisputed role as a primary regulator of gonadal function. It exerts this regulation by controlling the release of gonadotrophins. However, it is becoming apparent that GnRH may have a variety of other vital roles in normal physiology. A reconsideration of the potential widespread action that this traditional reproductive hormone exerts may lead to the generation of novel therapies and provide insight into seemingly incongruent outcomes from current treatments using GnRH analogues to combat diseases such as prostate cancer.     

High doses of salicylate and aspirin are inhibitory on acid-sensing ion channels and protective against acidosis-induced neuronal injury in the rat cortical neuron

Aspirin and its main metabolite salicylate are widely used to relieve pain, treat inflammatory diseases, and prevent ischemic stroke. Multiple pathways are responsible for the therapeutic actions exerted by these drugs. One of the pathways is targeting neuronal receptors/ion channels in the central nervous system. Correspondingly, increasing evidence has implicated acid-sensing ion channels (ASICs) in the processes of the diseases that are medicated by aspirin and salicylate. We therefore employed whole-cell patch-clamp recordings to examine the effects of salicylate as well as aspirin on ASICs in cultured cortical neurons of the rat. We recorded rapid and reversible inhibition of ASIC current by millimolar concentrations of aspirin and salicylate and found that salicylate reduced acidosis-induced membrane depolarization. These data suggest that ASICs in the cortex are molecular targets of high doses of aspirin and salicylate. In addition, the results from lactate dehydrogenase release measurement showed that high doses of aspirin and salicylate protected the cortical neuron from acidosis-induced neuronal injury. These findings may contribute to a better understanding of the therapeutic mechanisms of aspirin and salicylate actions in the brain and provide new evidence on aspirin and salicylate used as neuroprotective agents in the treatment of ischemic stroke.     

COX-1 and COX-3 inhibitors

Low doses of aspirin reduce both pain and fever, whereas the anti-inflammatory action of aspirin requires a much higher dose. It is possible that inhibition of cyclooxygenase (COX)-1 is the major action of aspirin involved in its analgesic and antipyretic effects, and inhibition of COX-2 is responsible for its anti-inflammatory action. We compared the analgesic effects of an aspirin-like drug (diclofenac) and a centrally acting analgesic (paracetamol) in the mouse stretching test and confirmed that the analgesic action of the aspirin-like drug was peripheral.

Two possible sites have been postulated for the antipyretic action of non-steroid anti-inflammatory drugs; (a) inhibition of COX in endothelial cells of hypothalamic blood vessels or (b) inhibition of COX synthesising prostaglandins near sensory receptors of sub-diaphragmatic vagal afferents. The antipyretic action of aspirin may be mediated by inhibition of COX-3 in hypothalamic endothelial cells or by inhibition of COX-1 localised close to sensory receptors of peripheral vagal afferents. It is also possible that both enzymes are involved in the antipyretic action of aspirin. Whereas lipopolysaccharide (LPS)-induced fever is attenuated in COX-2 gene-deleted mice, suggesting that COX-2 is responsible for this type of fever, the COX-1 gene may also be important in temperature regulation and in mediating the pyresis that occurs in the absence of infection.     

The mechanism of action of aspirin

The therapy of rheumatism began thousands of years ago with the use of decoctions or extracts of herbs or plants such as willow bark or leaves, most of which turned out to contain salicylates. Following the advent of synthetic salicylate, Felix Hoffman, working at the Bayer company in Germany, made the acetylated form of salicylic acid in 1897. This drug was named “Aspirin” and became the most widely used medicine of all time. In 1971, Vane discovered the mechanism by which aspirin exerts its anti-inflammatory, analgesic and antipyretic actions. He proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever. However, by inhibiting this key enzyme in PG synthesis, the aspirin-like drugs also prevented the production of physiologically important PGs which protect the stomach mucosa from damage by hydrochloric acid, maintain kidney function and aggregate platelets when required. This conclusion provided a unifying explanation for the therapeutic actions and shared side effects of the aspirin-like drugs. Twenty years later, with the discovery of a second COX gene, it became clear that there are two isoforms of the COX enzyme. The constitutive isoform, COX-1, supports the beneficial homeostatic functions, whereas the inducible isoform, COX-2, becomes upregulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis.     

17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy

Several types of motorneuron diseases are linked to neurotoxic mutant proteins. These acquire aberrant conformations (misfolding) that trigger deleterious downstream events responsible for neuronal dysfunction and degeneration. The pharmacological removal of misfolded proteins might thus be useful in these diseases. We utilized a peculiar motorneuronal disease model, spinobulbar muscular atrophy (SBMA), in which the neurotoxicity of the protein involved, the mutant androgen receptor (ARpolyQ), can be modulated by its ligand testosterone (T). 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) has already been proven to exert beneficial action in SBMA. Here we demonstrated that 17-AAG exerts its pro-degradative activity on mutant ARpolyQ without impacting on proteasome functions. 17-AAG removes ARpolyQ misfolded species and aggregates by activating the autophagic system. We next analyzed the 17-AAG effects on two proteins (SOD1 and TDP-43) involved in related motorneuronal diseases, such as amyotrophic lateral sclerosis (ALS). In these models 17-AAG was unable to counteract protein aggregation.     

Antiplatelet drugs: how to select them and possibilities of combined treatment

Antiplatelets are the pivotal drugs in preventing recurrent stroke or other major vascular events in patients who have undergone TIA or stroke. Aspirin is the most widely used, although its effect is very modest (relative risk reduction 20%), and most physicians use between 100 and 325 mg daily as a maintenance dose. For patients who develop stroke on aspirin treatment, the options are either to increase the dose of aspirin or to administer another anti-aggregate. No study has yet been performed to support these approaches. In patients who cannot tolerate aspirin, the options are clopidogrel 75 mg once daily or dipyridamole 400 mg combined with 50 mg aspirin. An approach which is very appealing, but not yet proven is to combine different antiplatelet drugs with different modes of action, such as aspirin and clopidogrel, in order to achieve a better and more effective antithrombotic effect. Further controlled trials are needed to justify this approach.     

Prevention of aspirin inhibition of platelet release reaction by the fatty acid precursor of platelet prostaglandins

Preincubating human platelet-rich citrated plasma with eicosatetraenoic acid (E-tetra), the immediate precursor of PGE₂ and F_2α, prevents the inhibitory effect of aspirin on the release reaction induced by epinephrine, ADP, thrombin or collagen. The methyl ester of E-tetra as well as a saline solution of arachidonyl C1 had the same effect as the free acid. In striking contrast to E-tetra, E-tri or its methyl ester, E-penta, stearic, oleic, linoleic and γ-linolenic acid failed to prevent the inhibitory effect of aspirin. Although E-tetra alone induces the release reaction, this phenomenon does not explain the action of E-tetra in blocking effects of aspirin. Thus, we tentatively postulate that E-tetra's unique protection of the platelet against the untoward effect of aspirin, may be attributable to the role it plays in platelet prostaglandin synthesis.     

Aspirin-associated intracerebral hemorrhage: clinical and radiologic features

OBJECTIVE: To identify the clinical and radiologic features of intracerebral hemorrhage (ICH) in aspirin users. BACKGROUND: Although the benefits of aspirin outweigh its hemorrhagic risks for patients at high risk of vascular diseases, prolonged use of aspirin is associated with an increased risk of ICH. METHODS: The authors enrolled consecutive patients with acute stroke who were admitted to a regional hospital from 1993 to 1998 into a stroke registry. From this registry, they identified all stroke patients who had ICH confirmed by CT scan and then selected those taking regular aspirin before ICH as the study group. For each study patient, they selected the immediate next two patients with ICH but not taking aspirin as controls. RESULTS: The authors identified 58 aspirin users and 1193 nonusers among all patients hospitalized for ICH. From the group of nonusers, they selected 116 patients as controls. The locations of the hematoma were different (p = 0.002), with more lobar hematoma in the aspirin group (32.8%) than in the control group (10.3%). Prior cerebrovascular disease was the reason for taking aspirin in 37 (64%) patients but five patients had prior ICH. CONCLUSIONS: The propensity for lobar hematoma in aspirin-associated ICH suggests its pathology may be somewhat different from spontaneous ICH among nonaspirin users. Further research to examine the risks and benefits of aspirin use in certain subgroups at risk of both thrombotic and hemorrhagic events is needed.     

阿司匹林与脑出血危险性的关系

目的 研究国人服用阿司匹林与脑出血危险性的关系.方法 采用临床病例回顾分析方法,以1986年1月～2003年12月收住院TIA患者及腔隙性脑梗死患者为研究对象,分为服药组与未服药组,以出现新的脑梗死或脑出血;发生急性心肌梗死、TIA或死亡;中止服药或截至观察时间结束时为观察终点,观察脑出血的发生情况.结果 小剂量阿司匹林服药组（25～100mg/d）与对照组脑出血发生率之间无明显差别,P=0.316＞0.05,RR=1.314,95%CI=0.771～2.242.中到大剂量阿司匹林服药组（300～900 mg/d）与对照组脑出血发生率之间有明显差别,P=0.000＜0.05,RR=4.610,95%CI=2.198～9.670.小剂量阿司匹林组与中到大剂量阿司匹林组之间有明显差别,P=0.000＜0.05,RR=3.602,95%CI=1.874～6.924.结论 TIA或腔隙性脑梗死患者服用小剂量阿司匹林进行2级预防不会增加脑出血的危险性,服用中等剂量到大剂量阿司匹林可以增加脑出血的危险性.