高血压患者凝血酶原纤溶酶原激活物和其抑制物测定

目的 探讨正常人各年龄组间和高血压病人血纤溶指标的差异及其意义。 方法 用发色底物法分别时≤３９岁（ｎ＝４９），４０￣５９岁（ｎ＝１４９），≥６０岁（ｎ＝６４）各组健康人和高血压组（ｎ＝５６）的血纤溶活性指标凝血酶原（ＰＬＧ），组织型纤溶酶原激活物（ｔ－ＰＡ）和纤溶酶原激活物（ｔ－ＰＡ）和纤溶酶原激活物抑制剂（ＰＡＩ）进行测定。 结果 ≥６０岁组和高血压组的ＰＬＧ和ｔ－ＰＡ明显低于５９岁以下各组（     

急性心肌梗塞患者纤溶指标的变化及其临床意义

对３２例急性心肌梗塞（ＡＭＩ）患者及３０例正常人的血浆纤溶酶原（ＰＬＧ）活性、组织纤溶酶原激活物（ｔ－ＰＡ）活性、纤溶酶原激活物抑制剂（ＰＡＩ）活性进行了检测。结果显示，ＡＭＩ组患者ｔ－ＰＡ活性显著低于对照组，ＰＡＩ活性、ＰＬＧ活性则高于对照组；ＡＭＩ组死亡者的ｔ－ＰＡ活性显著低于存活组；再发ＡＭＩ患者纤溶活性降低而纤溶抑制活性增强；ｔ－ＰＡ活性持久而明显降低，预示ＡＭＩ患者病情严重，预后不良，并     

原发性高血压伴脑腔隙性病变患者凝血和纤溶系统失衡的研究

目的进一步探讨高血压病患者合并脑腔隙性病变者与凝血纤溶系统之间的关系,为早期防治寻找依据。方法健康对照组３１例及观察组轻中度高血压病患者５８例（根据头颅核磁共振分为脑腔隙性病变组（ｎ＝４６）和非脑腔隙性病变组（ｎ＝１２）进行组织型纤溶酶原激活物（ｔ－ＰＡ）及其抑制物（ＰＡＩ）的活性、血管性假血友病因子抗原（ｖＷＦ：Ａｇ）和纤溶酶原（ＰＩＧ）活性、凝血因子Ⅷ促凝活性（Ⅷ：Ｃ）测定。结果（１）高血压病组与对照组各项指标比较：前组ｔ－ＰＡ、ＰＡＩ、ＰＬＧ明显高于后组（Ｐ＜０．０１）,两组ｖＷＦ：Ａｇ、Ⅷ：Ｃ无明显差别;（２）腔隙性病变组与对照组比较：ｔ－ＰＡ（Ｐ＜０．０１）,ｖＷＦ：Ａｇ（Ｐ＜０．０５）明显高于对照组,Ⅷ：ｃ无明显变化;（３）非腔隙性病变组与对照组比较：前组ｔ－ＰＡ（Ｐ＜０．０５）,ＰＡＩ（Ｐ＜０．０１）明显高于后组,两组ＰＬＧ、ｖＷＦ：Ａｇ无明显变化;（４）脑腔隙性病变组与非腔隙性病变组比较：各项指标均无明显差异。结论高血压病无论是否合并腔隙性病变均存在凝血和纤溶功能的失衡,提示早期预防具有重要意义     

早期糖尿病肾病血浆t—PA,PAI活性改变及其临床意义

早期糖尿病肾病血浆ｔ－ＰＡ、ＰＡＩ活性改变及其临床意义宋明强＊刘国良糖尿病肾病与凝血纤溶系统的相关性研究，近些年来极为人们所重视。本研究选用作为血液纤溶系统的关键成分——组织纤溶酶原激活物（ｔ－ＰＡ）和纤溶酶原激活物抑制物（ＰＡＩ）两项对应指标作为检...     

脂蛋白（a）与急性心肌梗塞纤溶功能的相关性及对溶栓疗效的影响

本文检测１２６例冠心病患者的脂蛋白（ａ）［ＬＰ（ａ）］和其他脂质，利用冠状动脉（冠脉）造影分析Ｌｐ（ａ）与３４例心绞痛患者冠脉狭窄的相关性，对３７例急性心肌梗塞（ＡＭＩ）溶栓疗效的影响和ＷＭＩ恢复期纤溶功能的关系。结果发现，Ｌｐ（ａ）与冠脉狭窄，较其他脂质有更高度相关性（ｒ＝０．４０１，Ｐ＜０．０１）。ＷＭＩ再通组ＬＰ（ａ）、纤溶酶原激活剂抑制物活性（ＰＡＩ：ａ）较未再通组低，组织型纤溶酶原激活剂活性（ｔ－ＰＡ：ａ）、ｔ－ｐＡ／ＰＡＩ、纤溶酶原活性（ＰＬＧ：ａ）较未再通组高。不论再通组、未再通组Ｌｐ（ａ）与ｔ－ＰＡ、ｔ－ｐＡ／ＰＡＩ、ＰＬＧ均呈负相关。     

PAI-1及其在血栓形成中的作用

纤溶酶原激活物抑制物１（ Ｐ Ａ Ｉ１） 是组织型纤溶酶原激活物（ｔ Ｐ Ａ） 的快速抑制物。ｔ Ｐ Ａ 与 Ｐ Ａ Ｉ１间的动态平衡对维持血浆纤维蛋白溶解系统（ 简称纤溶系统） 的稳态起决定性作用。 Ｐ Ａ Ｉ１ 水平已成为血栓形成性疾病的危险因素。文章综述了 Ｐ Ａ Ｉ１ 理化特性、 Ｐ Ａ Ｉ１ 基因多态性同血浆中 Ｐ Ａ Ｉ１ 水平相关性及 Ｐ Ａ Ｉ１水平和血栓形成的关系。     

t-PAA、PAIA活性测定在糖尿病肾病临床中的意义

目的：探讨糖尿病肾病（ＤＮ）临床中尿白蛋白排泄率（ＵＡＥＲ）与组织纤溶酶原激活物（ｔ－ＰＡＡ）、纤溶酶原激活物抑制物（ＰＡＩＡ）的相关性。地７１例糖尿病患者和３０例正常人的ＵＡＥＲ和ｔ－ＰＡＡ、ＰＡＩＡ进行测定,并对其相关性进行统计分析。结果：糖尿病组ｔ－ＰＡＡ随着ＵＡＥＲ的增高而降低,而ＰＡＩＡ则随着ＵＡＥＲ的增高而增高,糖尿病微量白蛋白尿组、临床蛋白尿组ｔ－ＰＡＡ与ＵＡＥＲ呈显著负相关（Ｐ〈０     

急性心肌梗塞尿激酶静脉溶栓治疗纤溶系统的变化及临床意义

观察４４例首次急性心肌梗塞（ＡＭＩ）患者的尿激酶（ＵＫ）静脉溶栓治疗前后血浆ＵＫ抗原、组织纤溶酶原激活物（ｔ－ＰＡ）抗原、纤溶酶原激活物（ＰＡ）活性、纤溶酶原激活物抑制物（ＰＡＩ）活性、纤溶酶活性和纤维蛋白原抗原的变化。结果显示：（１）ＵＫ静脉注射的作用持续时间较短，注射后１小时和５小时，分别有５３．２％和９３．７％的ＵＫ抗原从血浆中清除。（２）与治疗前相比，ＵＫ静注后ＰＡ和纤溶酶活性升高、ＰＡＩ活性降低，纠治了ＡＭＩ时纤溶系统的功能紊乱状况。但是，停止ＵＫ注射后即出现ＰＡＩ“反弹”现象，ＰＡ和纤溶酶活性随之降低，说明溶栓早期存在反常的高凝状态。（３）ＰＡＩ活性升高程度与左心室功能受损及ＡＭＩ病情程度有一定关系。以上各点均提示，溶栓早期辅助的抗凝治疗尤为重要。     

冠心病患者血液纤溶活性的改变

本研究测定了１４例急性心肌梗塞（ＡＭＩ）、１８例不稳定型心绞痛（ＵＡ）及２０例稳定型心绞痛（ＳＡ）及２０例正常人的血液组织型纤溶酶原激活剂（ｔ－ＰＡ）。纤溶酶原激活剂抑制物（Ｐａｌ－１）活性、纤溶酶原（ＰＬＧ）含量及纤溶酶（ＰＬ）活性。发现ＡＭＩ及ＵＡ发作时ＰＡＩ－１活性增高。ｔ－ＰＡ活性降低，ＰＬＧ含量升高，ＰＬ活性降低。表明ＡＭＩ及ＵＡ发作时纤溶活性低下，易诱发冠状动脉内血栓形成。此与ＡＭＩ及ＵＡ发生有密切关系。     

冠心病组织型纤溶酶原激活物及其抑制物的活性变化

冠心病组织型纤溶酶原激活物及其抑制物的活性变化邱建钱学贤刘映峰刘兰平我们比较了不同类型冠心病血浆组织型纤溶酶原激活剂（ｔＰＡ）和纤溶酶原激活剂抑制物（ＰＡＩ）活性的变化，并探讨ｔＰＡ和ＰＡＩ活性变化与冠状动脉（冠脉）病变范围和冠脉狭窄程度的关系。对象...     

Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade

The amyloid hypothesis states that a variety of neurotoxic beta-amyloid (Abeta) species contribute to the pathogenesis of Alzheimer's disease. Accordingly, a key determinant of disease onset and progression is the appropriate balance between Abeta production and clearance. Enzymes responsible for the degradation of Abeta are not well understood, and, thus far, it has not been possible to enhance Abeta catabolism by pharmacological manipulation. We provide evidence that Abeta catabolism is increased after inhibition of plasminogen activator inhibitor-1 (PAI-1) and may constitute a viable therapeutic approach for lowering brain Abeta levels. PAI-1 inhibits the activity of tissue plasminogen activator (tPA), an enzyme that cleaves plasminogen to generate plasmin, a protease that degrades Abeta oligomers and monomers. Because tPA, plasminogen and PAI-1 are expressed in the brain, we tested the hypothesis that inhibitors of PAI-1 will enhance the proteolytic clearance of brain Abeta. Our data demonstrate that PAI-1 inhibitors augment the activity of tPA and plasmin in hippocampus, significantly lower plasma and brain Abeta levels, restore long-term potentiation deficits in hippocampal slices from transgenic Abeta-producing mice, and reverse cognitive deficits in these mice.     

Staphylokinase reduces plasmin formation by endogenous plasminogen activators

Hyperfibrinolysis is a consequence of imbalance between fibrinolytic activators and their inhibitors. Increased levels of circulating plasminogen (Plg) activators such as tissue- or urokinase-type plasminogen activators (tPA or uPA respectively) are the most common causes of hyperfibrinolysis, occasionally causing major hemorrhages. We found that staphylokinase (SAK), a well-known Plg activator of bacterial origin, inhibits Plg activation mediated by endogenous tPA and uPA. Furthermore, mixture of SAK with tPA led to a significantly reduced Plg-dependent fibrinolysis. This inhibitory effect was exerted through direct action of SAK on Plg rather than indirectly on tPA or uPA. Inhibition of Plg activation by SAK is readily abrogated by interaction of SAK with human neutrophil peptides (HNPs). Finally, we show that NH2-terminal residues of SAK are important for the inhibitory effect of SAK on tPA- and uPA-mediated Plg activation. In conclusion, SAK reduces tPA/uPA-mediated Plg activation by means of SAK.Plg complex formation, consequently downregulating tPA/uPA-induced fibrinolysis.     

Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma

BACKGROUND AND METHODS: The plasminogen activation system plays a crucial role in the process of cancer invasion and metastasis. To evaluate the most effective factor in the invasion, metastasis and prognosis of hepatocellular carcinoma (HCC), we examined urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1, PAI-2 and uPA activity by enzyme-linked immunosorbent assays (ELISA) in HCC tissues obtained from 46 patients. The results were compared with the patients' clinicopathological features and prognoses. RESULTS: Of the clinicopathological features, only histological portal involvement or intrahepatic metastasis, or both (INV), was significantly correlated to the disease-free survival rates (DFS; P < 0.05). The levels of uPA, PAI-1 and PAI-2 antigens were significantly associated with INV and histological grade. The DFS was not different, however, between cases with uPA, PAI-1 and PAI-2 values above and below the median. The high levels of uPA activity were closely related to INV (P < 0.001), and the activity gradually raised histological grades (P < 0.0001). The DFS was significantly different between patients with uPA activity below and above the median (0.70 ng/mL; P = 0.0092); it was also significantly different between such patients without INV (P < 0.05). CONCLUSIONS: Urokinase-type plasminogen activator activity may be the most sensitive factor affecting HCC invasion in the plasminogen activation system and a strong predictor for the recurrence of HCC. We suggest that cases with uPA activity of more than 0.70 ng/mL should be carefully followed up for possible HCC recurrence.     

New strategies in the development of thrombolytic agents

Summary Recombinant DNA technology has allowed large-scale production of the physiological, fibrin-specific, plasminogen activators tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA). The results of clinical trials with these agents, mainly for the treatment of acute myocardial infarction, have revealed a limited fibrin specificity at the large therapeutic doses required for efficient thrombolysis. Mutants and variants of t-PA and scu-PA have given important information on structure-function relationships in these proteins and have resulted in rt-PA variants with significantly prolonged half-lives in vivo. Construction of chimaeric plasminogen activators containing various portions of t-PA and scu-PA has produced functionally active enzymes, however with a lower fibrin-affinity than wild-type t-PA. The promise of antibody targeting and the use of synergistic combinations of thrombolytic agents remains to be further investigated. We anticipate that eventually these research lines will yield artificial plasminogen activators with improved efficacy, risk/benefit and cost/benefit ratios.     

脑梗死患者血浆纤溶指标的动态观察

目的　探讨脑梗死患者血浆中纤溶分子标志物———组织纤维蛋白溶酶原激活剂 (TPA)和纤溶酶原激活物抑制剂 (PAI 1)含量的动态变化及其临床意义。方法　采用酶免疫定量法对 30例首次急性脑梗死患者急性期和恢复期的血浆TPA和PAI 1含量进行测定 ,并选择 30名正常人作为对照。同时对比首次急性脑梗死 30例和再发脑梗死 2 8例急性期血浆TPA及PAI 1含量。结果　首次急性脑梗死患者恢复期的TPA低于急性期 ,高于正常对照组 ;PAI 1含量脑梗死恢复期明显高于急性期。再次发病急性脑梗死患者比首次发病急性脑梗死患者的PAI 1高。结论　PAI 1与脑梗死的发生与发展有着重要关系 ,应作为临床的重要危险因素对待。     

Effect of a Change in the Sleep/Wake Cycle on the Diurnal Variation of Fibrinolytic Parameters

The mechanism underlying the circadian rhythm of fibrinolysis is not well understood. To evaluate the influences of wakefulness and of the intrinsic circadian rhythm on fibrinolytic activity, we examined diurnal changes (8:00 am vs. 8:00 pm) in plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator (t-PA) antigen levels, and t-PA activity, as well as in plasma serum cortisol levels, in 10 healthy males (21 ± 2 years) for two consecutive days. On the first day, subjects remained awake all day and night. They slept during the daytime (8:30 am to 5:30 pm) on the following day. PAI-1 activity and cortisol levels were significantly decreased, and t-PA activity tended to increase during the daytime on the first day. On the morning following overnight wakefulness, PAI-1 activity and cortisol levels did not return to the levels of the previous morning. On the second day, the afternoon decrease in PAI-1 activity, but not cortisol levels, was still observed, although its magnitude was substantially attenuated. No significant diurnal changes were observed in the levels of t-PA antigen throughout the study period. These findings suggest that the diurnal variation of fibrinolytic activity may be governed by an intrinsic circadian rhythm of PAI-1, which can be modified by a change in the time of wakefulness.     

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinasetype plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P<.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P<0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P<0.01), lymph node metastasis and depth of invasion (P<0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.     

Regulation of tissue plasminogen activator in sickle cell anemia

Evidence of activation of the clotting system in individuals with sickle cell anemia (SCA) has been observed by several investigators. It has been suggested that the clotting and fibrinolytic systems may play a role in the pathophysiology of vaso-occlusion in SCA. We reported previously evidence of abnormal fibrinolytic activity as reflected in decreased releasable tissue plasminogen activator (t-PA) using a functional assay. We have examined the mechanism of the decreased functional releasable t-PA in individuals with SCA. We studied 12 patients with respect to releasable t-PA, fast acting inhibitor to t-PA (or PAI-1), and immunoreactive or antigenic t-PA. These SCA individuals were at their baseline states and not taking medications known to interfere with the fibrinolytic or clotting systems. We found that the mean releasable t-PA for the SCA individuals was 0.01 IU/ml of plasma with a standard error of mean (SEM) of 0.01. The mean releasable t-PA of 118 healthy normal controls was 0.70 IU/ml with SEM 0.10 (P less than .001). The mean level of fast-acting inhibitor to t-PA in unoccluded circulation of the SCA patients' plasma was 16.5 IU/ml with SEM of 3.54. The mean plasma levels of fast-acting inhibitor to t-PA in 56 healthy controls was 2.56 IU/ml with SEM of 0.29 (P less than .0001). The SCA patients had a mean baseline t-PA antigen level of 5.98 ng/ml with SEM of 1.72. The mean level of t-PA antigen of 78 healthy controls using the same technique was 4.3 ng/ml with SEM of 2.7 (not significant). The mean baseline functional t-PA for SCA individuals was 0.15 IU/ml with SEM 0.01 and the mean baseline functional t-PA for 118 controls was 0.17 IU/ml with SEM 0.10. These data suggest that the mechanism of decreased releasable t-PA in sickle cell anemia is related to an elevation of fast-acting inhibitor to t-PA and that antigenically t-PA is present in normal quantities in the baseline plasma in this population.     

Evidence for an active fibrinolytic system in normal human bone marrow

Normal human bone marrow from patients undergoing heart surgery was analysed quantitatively for components of the fibrinolytic system, using functional and immunological assays. Marrow was found to contain considerable fibrinolytic activity, reflecting high levels of t-PA (tissue-type plasminogen activator). The t-PA was in an active form, despite the presence of the inhibitors PAI-1 and PAI-2. Plasminogen and α₂-antiplasmin (α₂-AP) were also present in marrow. The balance of proteases and inhibitors differed dramatically from that observed in plasma, with higher levels of t-PA, PAI-1 and PAI-2, and lower levels of u-PA (urokinase), plasminogen, α₂-AP and t-PA-PAI-1 complex in bone marrow, and resulted in favourable conditions for fibrinolysis. The presence of plasmin–α₂-AP complex at concentrations of the same order of magnitude as total plasminogen and α₂-AP demonstrated that active generation of plasmin was indeed occurring. A role for the active fibrinolytic system in normal human bone marrow may be the removal of unnecessary fibrin deposits formed in the cavities of the marrow, in order to maintain flow through this tissue.     

The Role of the Fibrinolytic System in Corneal Angiogenesis

The plasminogen activation system has been implicated in angiogenesis and angiogenesis-dependent diseases such as cancer, atherosclerosis and ocular diseases. The identification and development of inhibitors of angiogenesis offer new possibilities for the treatment of these diseases. To clarify the role of proteins involved in the regulation of fibrinolysis during corneal angiogenesis, we have studied corneal vessel formation in mice deficient for urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI). Our results corroborate earlier findings that angiogenesis in the mouse cornea is dependent on PAI-1 and plasminogen. The absence of tPA, uPA or TAFI did not affect the formation of new vessels in the cornea.