嗜麦芽寡养单胞菌蛋白酶纤溶活性及其机制的研究

目的自双齿围沙蚕消化道内分离得到1株嗜麦芽寡养单胞菌,前期研究发现该菌株可大量胞外分泌一种具有纤溶活性的蛋白酶。文中旨在观察嗜麦芽寡养单胞菌蛋白酶(S.maltophiliaprotease,SMP)在体内外的纤维蛋白溶解活性,并探讨其纤溶机制。方法试管凝块法和纤维蛋白平板法体外观察SMP对纤维蛋白和纤维蛋白原的溶解作用,计算其比活性;建立SD大鼠动-静脉旁路血栓模型,分别给予不同剂量的SMP、等渗盐水和蚓激酶,观察各组血栓重量及表面情况,检测血浆优球蛋白溶解时间(euglobulin lysis time,ELT)、纤维蛋白原(fibrinogen,Fg)、纤维蛋白降解产物(fibrin degradation prod-uct,FDP)和D-二聚体等指标,并比较血浆中组织型纤溶酶原激活物(tissue plasminogen activator,t-PA)和血浆纤溶酶原激活物抑制物-1(plasminogen activator inhibitor type-1,PAI-1)的变化。结果 SMP同时具有溶解纤维蛋白原和纤维蛋白的活性,且活性呈一定的量效关系;SMP不依赖纤溶酶原的激活而直接溶解纤维蛋白,并...     

中华眼镜蛇毒纤溶组份的纤溶活性及其机制研究

目的：研究中华眼镜蛇（NajaNajaatra）蛇毒中单一纤溶活性组份对人纤维蛋白和纤维蛋白原的降解作用及其机制。方法：使用剩余可凝纤维蛋白原测定法和酶联纤维蛋白原溶解试验研究该纤溶活性组份对人纤维蛋白原的降解作用；使用纤维蛋白平板法和酶联纤维蛋白溶解试验研究它对人纤维蛋白的降解作用；对它的纤溶机制研究使用的是纤维蛋白溶解酶原激活物活性测定法。结果：该活性组分对人纤维蛋白和纤维蛋白原有直接的降解作用。其活性大约是粗毒的10倍。该活性组份仅降解纤维蛋白原的Aa链，对它的印链和了链没有作用。该组分对人纤维蛋白溶解酶原没有激活作用。结论：从中华眼镜蛇毒中提取的单一纤溶活性组分是一种新的能够直接降解人纤维蛋白和纤维蛋白原的酶类。     

肝素和类肝素对大鼠纤溶活性的作用

大鼠腹腔注射类肝素-冠心舒200mg/kg后2h,优球蛋白溶解时间显著缩短,其促纤溶活性优于肝素;体外用药肝素与冠心舒对优球蛋白溶解时间无影响。实验结果还提示冠心舒与肝素的抗凝血活性与促纤溶作用不一致,抗凝效价不能代表促纤溶作用的强度。     

川芎嗪对凝血－纤溶系统酶活性的影响

实验以川芎嗪对凝血－纤维蛋白溶解系统酶活性的影响来探讨其活血化瘀机理．结果表明：川芎嗪对凝血过程中的凝血活酶和凝血酶的生成及活性有明显抑制作用，且抑制作用随浓度增加而加强；川芎嗪对纤溶酶原无直接激活作用，但能加速或增加尿激酶对纤溶酶原的激活作用或者增强纤溶酶对纤维蛋白的降解作用．因而川芎嗪对凝血－纤溶系统酶活性的影响是其活血化瘀机制的重要因素．     

川芎嗪对凝血—纤溶系统酶活性的影响

实验以川芎嗪对凝血－纤维蛋白溶解系统酶活性的影响来探讨其活血化瘀机理，结果表明，川芎嗪对凝血过程中的凝血酶和凝血酶的生成及活性有明显抑制作用，且抑制作用随浓度增加而加强，川芎嗪对纤溶酶原无直接激活作用，但对加速或增加尿激对纤溶酶原的激活作用或者增强纤溶酶对纤维蛋白的降解作用，因而川芎嗪对凝血－纤溶系统酶活性的影响是其活和因化瘀机制的重要因素。     

低分子肝素药物的临床应用

1 低分子肝素作用 低分子肝素(LMWH)是从标准肝素中分离出来的分子量较小片段,其功能有:抗FXa活性显著高于抗Fa活性,轻微抗凝活性(抗因子Ⅱ活性小于45 IU/mg),半衰期长,不明显延长KPTT,出血副作用小;有促进纤溶作用,可促进血管内皮细胞释放纤维蛋白溶解酶原激活剂和缩短优球蛋白溶解时间,故抗栓作用强;增强血管内皮细胞抗血栓作用而不干扰血管内皮细胞其他功能,故对出血和血小板功能无明显影响;有神经保护作用[1].     

赤子爱胜蚓纤溶酶的体外药理性质

用赤子爱胜蚓纤溶酶在体外分别测定对纤维蛋白平板试验和优球蛋白溶解试验的纤溶活性,发现它有促进纤维凝块的溶解作用。对血栓弹力图凝血和纤溶的动态观察,它主要的作用在于纤维蛋白溶解,而对凝血影响较小。对牛血管内皮细胞的实验初步结果表明,它有刺激血管内皮细胞释放t-PA的作用。用大剂量(25mg/kg体重)静脉注射进行小白鼠急性毒性试验,不引起出血和内脏损害。     

纤维蛋白溶解的细胞调节

在纤溶酶原系统的调节中,细胞表面的组织型纤溶酶原激酶(t-PA)与尿型纤溶酶原激酶(u-PA)受体所起的关键性作用已得到较详细证实。近年来研究显示,t-PA和纤溶酶原与纤维蛋白结合,并在其表面形成含纤溶酶的复合物,开始纤溶过程;此外,纤维蛋白表面还具有阻止已结合的纤溶酶被a_2-抗纤溶酶灭活的作用。这均提示纤维蛋白表面在纤维蛋白溶解的调节中也起着一定作用。下面就细胞表面纤溶酶原系统和纤溶酶原与细胞表面的相互作用作一概述。一、细胞表面纤溶酶原系统在过去5～6年里的研究发现,细胞纤维蛋白表面在调节纤溶酶原激活和调节纤溶酶     

尿激酶静脉溶栓治疗急性心肌梗死的护理

尿激酶直接作用于内源性纤维蛋白溶解系统,能催化裂解纤溶酶原成纤溶酶,后者不仅能降解纤维蛋白凝块,亦能降解血循环中的纤维蛋白原、凝血因子Ⅴ和凝血因子Ⅷ等,从而发挥溶栓作用。尿激酶对新形成的血栓起效快、效果好。尿激酶静脉溶栓治疗急性心肌梗死（以下称急性心梗）使冠脉再通的疗效已成为定论。     

PAI基础与临床研究进展

纤维蛋白溶解酶原激酶(Plasminogen Activator,PA)在血液纤维蛋白溶解系统的调节中起着十分重要的作用,其活性受到纤溶酶原激酶抑制物(Plasminogen Activator inhibitor,PAI)的控制。并已认识到纤维蛋白溶解过程主要与PAI水平和类型变化有关,对其在高危妊娠、血栓性疾病及溶栓治疗中的作用日趋受到重视。本文拟对PAI的研究进展作一综述。     

Effect of an extract of Paeonia lactiflora on the blood coagulative and fibrinolytic enzymes

Paeonia lactiflora with the action of promoting blood circulation and removing blood stasis had been shown to be able to inhibit thrombosis and platelet aggregation, increase fibrinolytic activity and promote thrombolysis. This paper described the influence of the extract of Paeonia lactiflora in vitro experiments on prothrombin time (PT), activated partial thromboplastin time (PTT), antithrombin effect, activity of plasminogen and urokinase. The experimental results showed that: (1) The extract of Paeonia lactiflora prolonged the time of PT and PTT. (2) The extract of drug was able significantly to inhibit the thrombin. (3) In study of fibrinolysis by fibrin standard plate experiments, the drug possessed activative effect on the plasminogen. (4) The activity of urokinase was reduced, while the extract of Paeonia lactiflora existed. The inhibitory effect on thrombin and effective effect on plasminogen of the drug might be an important mechanism of its action of promoting blood circulation and removing blood stasis.     

FIBRINOLYTIC ACTIVITY IN CORONARY HEART DISEASE

To evaluate the effects of the fibrinolytic system on the development of coronary heart disease (CHD), the level of released plasminogen activator was measured by venous occlusion in 60 CHD cases, and 20 healthy subjects. The level of plasma basic plasminogen activator activity, plasminogen, fibrinogen and serum fibrin degradation products (FDP) were determined also. In comparison with control subjects, a lower level of released plasminogen activator was found in all CHD patients, being especially marked in those with unstable angina pectoris and acute myocardial infarction. The levels of plasma plasminogen, fibrinogen and FDP were also significantly changed in these patients. In acute myocardial infarction patients, the level of released plasminogen activator was lower in cases complicated with heart failure than in those without.     

凝血纤溶失衡及炎性因子与冠状动脉粥样硬化性心脏病的关系研究进展

纤溶酶原激活物抑制物1(PAI-1)是调节血浆纤溶活性的关键因素。PAI-1水平升高导致纤维蛋白降解减少,从而引起血浆纤维蛋白原水平升高,血液呈高凝状态,有利于血栓形成。同时,炎性反应导致血管内皮受损,参与血栓形成。PAI-1、纤维蛋白原和炎性因子如白细胞介素6、肿瘤坏死因子α不仅在冠状动脉粥样硬化性心脏病的发病机制中发挥着重要作用,而且与冠状动脉粥样硬化性心脏病的预后有关。     

米非司酮对大鼠黄体和子宫内膜纤溶酶原激活因子的调节作用

采用纤维蛋白铺盖和放射免疫方法研究了米非司酮(RU486)对培养颗粒细胞及黄体细胞纤溶酶原激活因子(包括组织型tPA和尿激酶型uPA)的作用。结果示RU486能明显拮抗入绒毛膜促性腺激素(hCG)促进颗粒细胞tPA活性及孕酮分泌的作用。RU486和PGF2α能明显促进黄体细胞tPA分泌,但孕酮产生明显被抑制。用组织学培养的方法,结果表明,RU486能刺激妊娠子宫内膜tPA和uPA分泌。这些结果表明RU486的抗生育作用部分能通过PA起到抗排卵、溶黄体及抗早孕的作用。     

小儿肾炎患者纤溶功能的改变

对47例肾炎患儿进行t-PA:Ag、t-PA:A、PAI：A、D-Dimer、FDP-E和FDP共6项纤溶指标检测。结果提示：肾炎患儿存在明显纤溶活性升高；15例肾炎患儿经治疗后，随着症状改善，6项纤溶指标均恢复正常。提示：动态观察多项纤溶指标有助于肾炎患儿病情判断和疗效观察；FDP-E和D－Dimer相关分析表明，FDP-E可作为诊断肾炎患儿高凝状态的分子标志物之一。     

Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor

Fibrinolytic components after venous occlusion and concentrations of tissue plasminogen activator inhibitor were studied in 100 consecutive patients with confirmed recurrent deep vein thrombosis or pulmonary embolism. After 20 minutes of venous occlusion the fibrinolytic response was decreased in 33 patients, as measured both amidolytically with S-2251 and on fibrin plates. Two different mechanisms responsible for the poor fibrinolytic response could be distinguished. Twenty two of the patients in whom the response was poor released normal amounts of tissue plasminogen activator antigen, as assayed by immunoradiometric assay, but had appreciably increased concentrations of tissue plasminogen activator inhibitor. The 11 other patients in whom the response was poor had both low tissue plasminogen activator activities and low tissue plasminogen activator antigen concentrations but normal concentrations of tissue plasminogen activator inhibitor. The results show not only that defective synthesis or release of tissue plasminogen activator may be important in the pathogenesis of venous thrombosis but also that a large group of patients with thrombosis have an increased concentration of the inhibitor to tissue plasminogen activator.     

老年心力衰竭患者肾素-血管紧张素系统与纤溶活性变化的意义

目的探讨老年心力衰竭（HF）患者血浆肾素-血管紧张素系统（RAS）与纤溶活性的变化。方法老年HF患者46例（HF组）,非器质性心脏病住院患者18例（对照组）,取静脉血分别检测血浆纤溶酶原激活剂抑制物1（PAI-1）、组织纤溶酶原激活剂（t-PA）活性、血浆肾素活性（RA）及血管紧张素Ⅱ（AngⅡ）含量。结果老年HF患者血浆RA、PAI-1活性、AngⅡ含量明显高于对照组（P〈0.05）,t-PA活性则降低（P〈0.05）;血浆PAI-1活性与AngⅡ含量水平呈显著正相关（r=0.396,P〈0.01）。结论老年HF过程中血浆RAS激活对纤溶活性改变有重要影响。     

Blood clotting and fibrinolysis in pregnancy.

During normal pregnancy, the concentrations of many of the clotting factors rise, thereby increasing the potential to generate fibrin. There is also evidence of increased thrombin activity during normal pregnancy which sharply increases during placental separation. Antithrombin III, the main inhibitor of thrombin and activated factor X, shows no compensatory rise during pregnancy but increases during the puerperium. Plasminogen and antiplasmin concentrations rise during pregnancy but systemic fibrinolytic activity, as measured by the euglobulin lysis time, is markedly depressed during pregnancy; the reduced fibrinolytic activity returns to non-pregnant values very soon after delivery. The loss of fibrinolytic activity is presumed to be loss of plasminogen activator, because when this is added in excess in the urokinase sensitivity test, the fibrinolytic response is normal. The capacity for localized fibrinolytic activity is not lost, however, because fibrinolytic degradation products are slightly raised during pregnancy. The overall pattern is one of increased coagulant and reduced fibrinolytic capacity during pregnancy which may protect the pregnant woman against the haemostatic challenge of placental separation.     

龙蛭胶囊体内外对动物凝血、纤溶功能的影响

目的:探讨龙蛭胶囊对动物体内外抗凝血、纤维蛋白溶解的作用。方法:按试剂盒说明对龙蛭胶囊进行活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)含量的测定。用常规方法测定体外凝血时间(CT)、血块溶解时间(BLT)、优球蛋白溶解时间(ELT)。采用纤维蛋白平板法测定龙蛭胶囊纤溶活性。结果:龙蛭胶囊能明显延长动物APTT、PT、TT,降低FIB含量。动物的BLT、ELT与生理盐水对照组比较明显缩短,差异均有统计学意义(P<0.05或P<0.01)。在普通纤维蛋白平板和加热平板上能溶解纤维蛋白。结论:龙蛭胶囊具有抗凝作用,能直接溶解纤维蛋白。