卡托普利对家兔急性心肌梗塞早期血小板活化及纤溶活性的影响

本研究观察了家兔急性心肌梗塞（ＡＭＩ）早期血浆血小板α－颗粒膜蛋白（ＧＭＰ－１４０）、血栓素Ｂ２（ＴＸＢ２）、组织型纤溶酶酶原激活剂（Ｔ－ＰＡ）及其抑制物（ＰＡＩ－１）水平的变化及卡托利干预的ＰＡ活性显著降低；相关分析表明，血浆ＧＭＰ－１４０浓度与ＰＡＩ－１活性显著正相关。卡托普利干预后，血浆ＧＭＰ－１４０浓度、ＴＹＸＢ２浓度、Ｔ－ＰＡ浓度、ｔ－ＰＡ含量、ＰＡＩ－１活性均明显降低，而ｔ－ＰＡ活性显     

人参皂甙对大鼠心肌缺血再灌注时纤溶活性变化的影响

本文应用Ｌａｎｇｅｎｄｏｒｆｆ无作功循环式离体心脏灌流技术、结扎左冠脉前降支造成急性心肌梗塞模型，以冠脉流出液和血浆为标本，观察人参皂甙对缺血再灌注损伤时纤溶活性变化的影响。结果显示，离体心脏停灌４５ｍｉｎ或再灌１５ｍｉｎ后，组织型纤溶酶原活化物（ｔ－ＰＡ）活性呈明显降低（与正常灌注相比Ｐ分别＜０．０５，０．０１），预灌注人参皂甙后，ｔ－ＰＡ活性可恢复到缺血以前的水平。人参皂甙２００ｍｇ／ｋｇ一次     

组织纤溶酶原激活剂及其抑制物的研究进展

纤溶酶原转变成有纤溶活性的纤溶酶是纤溶过程中决定性的一步。组织型纤溶酶原激活剂（ｔｉｓｓｕｅｔｙｐｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒ,ｔＰＡ）是体内主要的纤溶酶原激活物,而纤溶酶原激活剂抑制物（ｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒｉｎｈｉｂｉｔｏｒ,ＰＡＩ）是组织型纤溶酶原激活剂（ｔＰＡ）的快速抑制剂。近年来国内大量的研究发现,ｔＰＡ、ＰＡＩ活性或含量的变化与许多疾病,特别是心、脑血管疾病密切相关,已引起专家学者日益广泛的重视［１,２］。本文就组织纤溶酶原激活剂及其抑制剂的分子…     

犬急性心肌缺血对内源性纤溶功能的影响

用缩窄犬冠脉致急性心缺血动物模型，动态观察血浆纤维蛋白原，组织型纤溶酶原激活剂及其抑制物、血栓素Ｂ２，６－酮前列纱Ｆ１级血浆肾素活性、血管紧张素Ⅱ水平的变化。结果表明：ＡＭＩ１５ｍｉｎ后，血浆ＰＡＩ、ＴＸＢ２及ＡＮＧⅡ水平随缺血时间延长逐渐渐增加。６０ｍｉｎ高峰，３０ｍｉｎ时血浆ｔ－ＰＡ活性水平开始降低，６０ｍｉｎ达低峰值，；６０ｍｉｎ后，血浆Ｆｅ及ｔ－ＰＡ含量显著增加，提示ＡＭＩ可能主要通过激活     

大鼠心肌缺血及再灌时血浆蛋白C的变化

复制大鼠心肌缺血再灌模型，观察血浆抗凝因子蛋白Ｃ（ＰＣ）的活性变化及血浆ＰＡＩ和ｔ－ＰＡ的活性，同时监测心电图、血清ＬＤＨ、ＳＧＯＴ和心脏病理学改变。结果表明，心肌缺血时ＰＣ活性明显降低（与对照组比Ｐ＜０．０５），随着缺血时间延长，ＰＣ活性呈现进一步下降。此外，ｔ－ＰＡ活性的变化规律与ＰＣ相同，ＰＡＩ则与ＰＣ相反。缺血再灌后ＰＣ、ｔ－ＰＡ和ＰＡＩ活性都略有恢复。提示，ＰＣ活性降低参与急性心肌梗塞（     

金纳多治疗脑梗塞的疗效观察

目的：观察金纳多治疗脑梗塞病人的临床疗效及血液流变学指标和血管活性物质的变化,了解金纳多治疗脑梗塞的作用机理。方法：脑梗塞病人每日采用金纳多注射液２０ｍｌ加入到０．２％盐酸培他啶５００ｍｌ,静脉滴注２个疗程。同时对照观察患者血液流变学及血浆中ＴＸＢ２、６－ｋｅｔｏ－ＰＧＦ１α、ＥＴ、ＣＧＲＰ、ｔ－ＰＡ、ＰＡＩ等血管活性物质的变化。结果：金纳多组总有效率９０％,显效率７５％。对照组总有效率８３％,显效率４０．４％。金纳多组血液流变学指标改善显著。缩血管活性物质显著下降,舒血管活性物质显著升高;血浆组织型纤溶酶原激活剂（ｔ－ＰＡ）的活性升高,纤溶酶原激活剂抑制物（ＰＡＩ）的活性降低。结论：金纳多具有协同培他啶增加脑组织微循环血流、提高脑组织氧供应和防止脑组织损伤等作用,可以作为治疗脑梗塞的辅助药物。     

运动对冠心病患者血浆纤溶活性的影响及其临床意义

为探讨冠心病患者血浆纤溶活性变化及其与冠脉病变程度的关系。本文比较了冠心病组和正常对照组在桨极量运动前后血浆组织型纤溶酶的激活物（ｔＰＡ）,纤溶酶原么物抑制剂－１（ＰＡＩ－１）活性的变化。及其与心肌缺血面积的相关性。结果显示：（１）运动前冠心组ｔＰＡ及ＰＡＩ－１活必闹于正常对照组（Ｐ〈０．０５）,运动后冠心病组ＰＡＩ０－１活性明显升高（Ｐ〈０．０５）,而ｔＰＡ活性水平明显下降（Ｐ〈０．０５）;（２     

Iloprost对内皮细胞抗血栓功能的影响

以体外培养的猪主动脉内皮细胞（ＥＣ）为模型研究Ｉｌｏｐｏｓｔ对ＥＣ抗血栓功能的影响。用放免法、发色底物法测定培养液中６－酮－ＰＧＦ１α（６－ｋｅｔｏ－ＰＧＦ１α），血栓素Ｂ２（ＴＸＢ２）含量，纤溶酶原激活物（ＰＡ），纤溶酶原激活物抑制物（ＰＡＩ）活性及ＥＣ环磷酸腺苷（ｃＡＭＰ）含量。结果表明：Ｉｌｏｐｒｏｓｔ中以使ＥＣ生成６－ｋｅｔｏ－ＰＧＦ１α，ｃＡＭＰ含量显著增多，ＴＸＢ２含量显著减少，并使Ｐ     

肿瘤坏死因子α和轻度氧化低密度脂蛋白对人脐静脉 内皮细胞PAI-1活性的影响及机制

目的和方法 :自本世纪八十年代以来 ,纤维蛋白原及纤维蛋白形成和降解都参与动脉粥样硬化的发生、发展已逐渐为人们认识。在血管系统中 ,纤维蛋白的降解过程主要由纤溶酶原激活物 (ｔ-ＰＡ)启动。纤溶酶原激活物抑制剂 (ＰＡＩ - 1 )是ｔ-ＰＡ的生理性抑制剂 ,和ｔ-ＰＡ结合后可抑制其活性 ,是纤溶系统功能活性的重要调节因子。体内外实验均表明 ,在炎症及动脉粥样硬化相关致病因子的作用下 ,ＰＡＩ - 1活性及浓度显著增高。ＰＡＩ- 1活性增高影响了血浆凝血和纤溶系统的平衡 ,易形成血栓。动脉硬化致病因子致ＰＡＩ- 1浓度及活性增高可能是…     

高血脂对纤溶系统活性的影响

高 脂血症是一种常见的代谢性疾病 ,是高血压、动脉粥样硬化和冠心病的重要病因之一。研究表明血脂的上升会引起血液粘稠度增高 ,导致凝血系统发生相应改变 ,严重时会形成血栓。为探讨高脂血症与凝血系统的相关关系 ,我们对高脂血症患者血浆组织型纤溶酶原激活剂 (ｔ ＰＡ)和纤溶酶原激活剂抑制物 (ＰＡＩ)活性进行测定 ,从而了解高脂血症与ｔ ＰＡ和ＰＡＩ活性的相关关系。1　资料与方法1.1　受检对象高脂血症组 :我们在临床上选择血清总胆固醇 (ＴＣｈ) >5 .8ｍｍｏｌ/Ｌ或 /和甘油三酯 (ＴＧ) >1.71ｍｍｏｌ/Ｌ者 35例视为高脂血症组 ,平…     

On the usefulness of fibrinolysis variables in the characterization of a risk group for myocardial reinfarction

In a prospective study selected fibrinolysis variables were assessed in plasma samples from 29 consecutive patients recovering a first instance of acute myocardial infarction and the results were correlated with reinfarction during the next four years. Nine patients suffered a reinfarction leaving a group of 20 patients without evidence of relapse. The reinfarction group was characterized by lower tissue plasminogen activator activities in plasma euglobulins (p less than 0.05), significantly higher plasma concentrations of tissue plasminogen activator antigen (p less than 0.002) and a tendency to a higher plasma level of plasminogen activator inhibition capacity. There were no significant differences between the groups in plasma concentrations of plasminogen, histidine-rich glycoprotein, plasminogen kringle-4-binding-protein, and alpha 2-antiplasmin.     

Untersuchung zur Frage von persistierenden Veränderungen der Fibrinolyseparameter t-PA und PAI bei Patienten nach juvenilem ischämischen cerebralem Insult

Summary In diseases associated with thrombotic or thromboembolic complications, a reduction in the fibrinolytic potential may contribute to the risk to develop thrombosis.To investigate whether iuvenile cerebral infarction is associated with a permanent defect of the fibrinolytic system we measured the main components of the fibrinolytic system, tissue plasminogen activator (t-PA) and its fast acting inhibitor (PAI) in plasma samples of 21 patients (aged 21–44 years) 3–24 months after the acute event. The data obtained were compared to those from thirteen healthy young volunteers (22–46 years). A direct effect of known risk factors on the fibrinolytic system could be excluded because patients avoided their risk factors immediately after the ischemic cerebral attack. Hypertension and the combination of oral contraceptives and smoking had been the most striking original risk factors.Levels of t-PA antigen and t-PA activity before and after venous occlusion, or PAI activity were not different between patients and controls suggesting that at least a permanent decrease in the activity of the fibrinolytic system does not exist in these patients. However, our findings do not exclude that a temporary defect in fibrinolysis might have contributed to the acute onset of the thrombotic cerebral event possibly induced by the risk factors originally present.

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Abkürzungen t-PA tissue plasminogen activator - PAI plasminogen activator inhibitor - RIND reversibles ischämisches neurologisches Defizit - KS kompletter Schlaganfall - TIA transitorisch ischämische Attacke     

蚓激酶（普恩复）治疗脑梗塞时抗凝和纤溶变化的临床研究

目的：探讨蚓激酶（普恩复）治疗急性脑梗塞时抗凝和纤溶的变化。方法：随机选择31例脑梗塞例患者，服药前后对患者行神经功能缺失评分、血浆中KPTT、PT、FIB、t－PA、PAI、D－二聚体的测定，并与以丹参治疗的20例脑梗塞患者进行对照。结果：患者口服蚓激酶后（400mg，3次／日），KPTT明显延长（P＜0．05），FIB明显减少（P＜0．05），t－PA活性明显增强（P＜0．01），D－二聚体明显增加（P＜0．01），以上指标在对照组中治疗前后无明显变化（P＞0．05）。治疗组、对照组PT、PAI在用药前后均无明显变化（P＞0．05）。结论：蚓激酶治疗脑梗塞取得疗效与内凝血途径抑制、纤溶的激活有关。     

Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction

Certain risk factors for myocardial infarction have been linked with disturbances in fibrinolytic activity. The recent development in our laboratory of new sensitive and specific methods for determination of tissue plasminogen activator (t-PA) activity and antigen, as well as the discovery of a new rapid inhibitor of this enzyme, enabled us to study fibrinolytic function in detail in a representative population of postinfarction patients. Seventy-one patients (62 men and 9 women) who had survived a myocardial infarction before the age of 45 were compared with 50 healthy subjects of similar age, three years after the infarction. Low t-PA activity after venous occlusion, mostly explained by high plasma levels of the t-PA inhibitor and to some extent by impaired release of t-PA from the vessel wall, was a frequent finding in the patients. The level of t-PA inhibitor was positively and significantly correlated with levels of serum triglycerides. Our data suggest that reduced fibrinolytic capacity due to increased plasma levels of a rapid inhibitor of t-PA may have pathogenetic importance in myocardial infarction, particularly in patients with hypertriglyceridemia.     

Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 levels in acute myocardial infarction

The cause of the circadian variation in the incidence of acute myocardial infarction (AMI) has not been identified. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) have opposing effects on thrombi. Hence, the extent of the clot, the size of the infarct and outcome of patients could depend on t-PA and PAI-1 levels. In an effort to elucidate the pathophysiologic basis of circadian variation of AMI, we investigated the presence of a possible corresponding circadian variation in the levels of endogenous t-PA and PAI-1 in patients diagnosed to have AMI and the effects of hypertension, diabetes and site of the infarct on these levels. We estimated the levels of t-PA and PAI-1 in platelet-poor plasma of 42 patients with AMI on admission, using the enzyme-linked immunosorbant assay. Although not statistically significant, patients having an AMI in the morning hours had the highest t-PA:PAI-1 ratio. The normal circadian variation in PAI-1 levels was lost in patients with AMI, probably due to the disease process. Also, the t-PA levels in hypertensive patients were significantly lower than in nonhypertensives. PAI-1 levels were also significantly lower in patients with anteroseptal than in inferior and anterolateral AMI. This relationship between the fibrinolytic potential and the site of infarction needs further study. Furthermore, t-PA levels on admission were significantly lower in survivors and may have a predictive value in determining the outcome.     

Effects of a long-term pharmacological interruption of the renin-angiotensin system on the fibrinolytic system in essential hypertension

To assess the effects of pharmacological interruption of the renin-angiotensin system on the fibrinolysis, tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor-1 antigens (PAI-1) and neurohormones, such as plasma renin activity, norepinephrine, angiotensin II (AII) and IV (AIV) concentrations, were measured in 60 hypertensives. Among them, 48 patients were divided into two groups (25 with 10-20 mg quinapril and 23 with 50-100 mg losartan) who received the drug for 6 months. AII had a weak positive correlation with free PAI-I (n = 60, r = 0.26, p < 0.05) whereas AIV had a strong positive correlation with free PAI-I (n = 60, r = 0.57, p < 0.0001). In both treatment groups, blood pressures were significantly reduced to similar levels after drug treatment. While plasma renin activity increased significantly in both groups after drug treatment, only the losartan group showed significant increases in AII and AIV concentrations. In the quinapril group, there was a significant change in t-PA (p < 0.001) without changes in PAI-1. In the losartan group, free PAI-I and total PAI-I (p < 0.05 for free PAI-I and p < 0.04 for total PAI-I) were significantly increased without a change in t-PA. Thus, quinapril enhanced fibrinolysis but losartan attenuated it. These unique effects of each drug on the fibrinolytic system appear to be associated with changes in AII and AIV concentrations.     

Prothrombin activation by thrombolytic agents

Previous studies showed an early increase of fibrinopeptide A and thrombin-anti-thrombin III complex (TAT) plasma levels during thrombolytic therapy. This might be caused not only by liberation of preformed thrombin from the thrombus or reperfused tissue, but also by activation of prothrombin.In 11 patients with acute myocardial infarction treated with 1.5 million U streptokinase (SK) over 30 min, and in 6 patients with deep vein thrombosis receiving standard dose urokinase (UK) infusion, TAT and the prothrombin fragment F1+2 increased significantly 3h after commencing thrombolytic therapy, and decreased again thereafter.In vitro, TAT and F1+2 levels increased in anticoagulated normal plasma after incubation with SK, UK or tissue-type plasminogen activator (t-PA). By incubation of purified prothrombin with SK+plasminogen (PLG), UK, UK+PLG, t-PA, t-PA+PLG, or plasmin, F1+2 immunoreactivity was generated. Also the generation of thrombin-like activity from purified prothrombin could be demonstrated by means of a chromogenic substrate assay with inhibition of non-specific cleavage by purified plasminogen activator inhibitor type 2 (PAI-2) or α₂-antiplasmin (APL).These results demonstrate an activation of prothrombin associated with stimulation of fibrinolysis. Further studies should clarify the clinical significance of this phenomenon, and whether it could have implications for optimizing the concomitant anticoagulation in order to prevent reocclusion in patients undergoing thrombolysis.     

脂蛋白的氧化修饰对血凝及纤溶活性的影响

目的:研究脂蛋白的氧化修饰对凝血及纤溶活性的影响。方法:用Cu²⁺法及次氯酸法氧化修饰超速离心分离的正常人血浆极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL)。分别将天然及氧化修饰脂蛋白N-VLDL、Ox-VLDL;N-LDL、Ox-LDL、N-HDL及Ox-HDL加入由正常人新鲜混合血浆构成的反应系统中,以相应天然脂蛋白为对照,测定凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、组织型纤溶酶原激活物(t-PA)活性、纤溶酶原激活物抑制剂1(PAI-1)活性及血小板最大聚集率。结果:VLDL、LDL及HDL经Cu²⁺法及次氯酸法氧化修饰后其REM、234nm吸光度值、TBARS含量均显著大于对照组(P<0.01)。Ox-VLDL、Ox-LDL及Ox-HDL使PT及APTT明显短于对照组(P<0.05或P<0.01),血小板聚集率明显高于对照组(P<0.01)。Ox-VLDL及Ox-LDL使t-PA活性高于对照组,PAI-1活性低于对照组(P<0.05及P<0.01),而Ox-HDL对t-PA活性及PAI-1活性的影响与对照组无明显差别。结论:N-VLDL、N-LDL及N-HDL对凝血及纤溶活性无影响。Ox-VLDL、Ox-LDL及Ox-HDL促进血凝及血栓形成;Ox-VLDL及Ox-LDL使纤溶活性增加,而Ox-HDL对纤溶活性无明显影响。