Effects of black cohosh on the plasminogen activator system in vascular smooth muscle cells

Objective

The rhizome of the Cimicifuga racemosa plant (commonly known as black cohosh) has been used for menopausal complaints. Studies regarding the cardiovascular effects of black cohosh are lacking. We investigated the effect of black cohosh on the plasminogen activator system in cultured vascular smooth muscle cells (VSMCs).

Methods

VSMCs were isolated from rat aortae. Expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) proteins were evaluated by Western blot analysis and enzyme-linked immunosorbent assay, respectively. The activities of PAI-1 and t-PA in the conditioned media were assessed by fibrin overlay zymography. A 40% 2-propanol extract of black cohosh was used.

Results

Black cohosh extract (BcEx) stimulated the protein expression of PAI-1, but it did not affect that of t-PA. Vitamin E, a potent antioxidant, inhibited the BcEx-induced increase in PAI-1 expression, while ICI 182,780, an estrogen receptor antagonist, had no effect. Fibrin overlay zymography revealed that BcEx increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA by inducing a binding to PAI-1.

Conclusions

BcEx induces PAI-1 protein expression in the VSMCs likely via an oxidant mechanism. It also stimulates the enzyme activity of PAI-1 and reduces that of free t-PA. These findings suggest that black cohosh might exert a negative influence on fibrinolysis.     

Detection of vitronectin by ligand blotting with type 1 plasminogen activator inhibitor

Ligand blotting procedures were developed for the detection of type 1 plasminogen activator inhibitor (PAI-1) binding protein(s) (BPs) transferred to nitrocellulose sheets after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Purified vitronectin (Vn), a well characterised PAI-1 BP, was employed to optimise this assay system. After blocking with casein, the sheets were washed and then incubated with either ¹²⁵I-labelled PAI-1 (direct assay), or with unlabelled PAI-1 followed by a polyclonal antiserum to PAI-1 (indirect assay). In the latter case, the bound antibody was detected by using an ¹²⁵I-labelled second antibody. Binding was dose-dependent with respect to both Vn and PAI-1, and only active PAI-1 bound to Vn (i.e. latent PAI-1 and PAI-1 in complex with tissue-type plasminogen activator (t-PA), did not bind to Vn in this system). Moreover, t-PA, arginine and acidic conditions dissociated PAI-1 from Vn adsorbed to nitrocellulose. Analysis of bovine plasma by these techniques revealed the presence of a single PAI-I BP, and this protein was recognised by antisera to Vn. These results indicate that Vn previously fractionated by SDS-PAGE and transferred to nitrocellulose, continues to bind to PAI-I in a manner that resembles its behaviour in plasma and on extracellular matrix. These ligand blotting procedures may thus represent useful new approaches for the detection of other SDS-stable PAI-1 binding proteins in biological samples.     

Detection of specific forms of plasminogen activator inhibitor type 1-by monoclonal antibodies

Monoclonal antibodies to plasminogen activator inhibitor type-1 (PAI-1) were generated and characterised for their ability to inhibit PAI-1 interaction with tissue plasminogen activator (t-PA) and urokinase (u-PA) and detection of the various forms of PAI-1 (native, complexed, and degraded) by immunoblotting. Mab17 inhibited both complex formation between PAI-1 and t-PA/u-PA and PAI-1 activity in a dose dependent manner by 90%. Mab 25 was much less effective, blocking complex formation less than 30% and PAI-1 activity less than 20%. The Kds of Mab 17 and Mab25 were 2.8×10⁻¹¹ M and 2.6×10⁻¹⁰ M, respectively. Following SDS-PAGE and immunoblotting, Mab 17 detected native PAI-1 only; PAI-1 in complex and the t-PA/u-PA degraded form of PAI-1(M_r=42000) did not react with this antibody. In contrast, Mab25 detected all three forms of PAI-I although the affinity for the native form appeared to be greater than Mab 17 or the PAI-1 polyclonal employed. Despite these differences, both monoclonal antibodies immunoprecipitated native and degraded PAI-1 equally as well. These results suggest that the epitope of Mab 17 is associated with the reactive site of PAI-1 and that this region is either missing or not accessible in the cleaved form or in complex.     

Influence of aging and circadian fluctuation of fibrinolytic factors to the responses of these factors during venous occlusion test in healthy subjects]

This study was aimed to clarify the influence of aging and circadian fluctuation of fibrinolytic factors to changes of tissue plasminogen (t-PA) and its inhibitor (PAI-I) during venous occlusion test. Venous occlusion was achieved by application of a sphygmomanometer cuff to the upper arm of elderly healthy subjects (n = 12) and young healthy subjects (n = 12) at 10:00 am and 4:00 pm. Plasma concentration of t-PA, free PAI-1 and total PAI-1 were measured by ELISA. The activity of t-PA was measured by bioimmunoassay using monoclonal antibody for t-PA. Circadian variation was observed in the change of t-PA activity and total PAI-1. These were highly increased in the evening. However, this phenomenon was different between age groups and increase of t-PA activity occurred in elderly subjects, whereas PAI-1 was observed in young subjects. In conclusion, circadian variation and the influence of age should be considered to evaluate results of venous occlusion test.     

Tissue plasminogen activator, plasminogen activator inhibitors, and activator-inhibitor complex in liver disease.

AIMS--To identify the relative contribution of plasminogen activators, particularly tissue plasminogen activator (t-PA) and specific plasminogen activator inhibitors (PAI-1, PAI-2), to the fibrinolytic changes associated with various types of liver disease or severe chemical and physical damage to the liver. METHODS--Platelet rich (PRP) and platelet poor plasma (PFP) from patients with alcoholic cirrhosis, primary biliary cirrhosis, hepatic malignancy, or paracetamol overdose, or who were undergoing partial hepatectomy or liver transplantation, were assayed for t-PA, PAI-1, t-PA-PAI-1 complex and PAI-2 antigen values using specific enzyme linked immunosorbent assays (ELISAs) developed in this laboratory. RESULTS--Appreciable increases in the plasma concentration of t-PA, PAI-1, and t-PA-PAI-1 were seen in patients with alcoholic cirrhosis, primary biliary cirrhosis, and hepatic malignancy. Liver damage due to paracetamol overdose and partial hepatectomy both resulted in a striking increase in plasma PAI-1 concentration, although concentrations of t-PA and t-PA-PAI-1 complex were less affected. Concentrations of t-PA, PAI-1, and t-PA-PAI-1 complex returned to near normal values after successful liver transplantation in a patient with chronic active hepatitis. PAI-2 was also detected in several patients with chronic liver disorders. CONCLUSIONS--Haemorrhage due to fibrinolytic bleeding is commonly associated with liver disease. The patients studied here all had appreciable increases in circulating t-PA antigen concentrations. This was associated with increased concentrations of PAI-1 antigen and t-PA-PAI-1 complex and the balance between activator and inhibitor did not result in systemic plasmin generation. Reduced PAI-1 activity in cirrhosis or a critical difference in the ratio of t-PA to PAI-1 concentrations may explain the enhanced plasminogen activator activity previously noted in cirrhosis but not metastatic disease. Reduced hepatic clearance of t-PA and t-PA-PAI-1 complex due to impaired liver function may account for increased concentrations of free and complexed t-PA.     

The activation of plasminogen by tissue plasminogen activator is not enhanced by different heparin species as assessed in vitro with a solid-phase fibrin method

The aim of this study was to evaluate the effect of several heparin species (standard heparin, heparin of low molecular weight: IC 831422, heparin of high affinity for antithrombin III: IC 831435, and heparin of low affinity for antithrombin III: IC 831436) on the different steps of the fibrinolytic mechanism i.e., interaction of tissue-type plasminogen activator (t-PA) with plasminogen activator inhibitor-1 (PAI-1), binding of t-PA and plasmin(ogen) to fibrin and activation of plasminogen on the fibrin surface, in the presence of plasma proteins and factors that modulate fibrinolysis. Fibrinolytic and plasmin amidolytic activities were measured in the presence and absence of heparin. The spectrophotometric assays were performed in the presence and absence of solid-phase fibrin using selective chromogenic substrates for plasmin and saturating concentrations of plasminogen.The overall fibrinolytic activity, the amidolytic activity of mixtures of t-PA or urokinase with plasminogen in the absence of fibrin, the binding of t-PA and plasmin(ogen) to fibrin and the t-PA/PAI-1 interaction were not modified by heparin. In contrast, the activation of plasminogen by fibrin-bound t-PA decreased as a function of the concentration of heparin. Although this effect was not significant at concentrations usually used in routine heparin therapy (0.1 to 1 iu/ml) it might have some relevance when heparin is injected in bolus doses.In conclusion, by using a solid-phase fibrin method which allows the analysis of t-PA/PAI-1 balance, data were obtained indicating that the heparin species tested here neither competed with fibrin for the binding of t-PA, nor potentiated the activation of plasminogen at the fibrin surface.     

Plasminogen activator inhibitor-1 deposition in the extracellular matrix of cultured human mesangial cells.

Human mesangial cells secrete tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), the latter being secreted in large excess in vitro. We demonstrate that PAI-1 is a major component of the extracellular matrix of cultured human mesangial cells, where its deposition is dependent on cell density. By immunogold silver staining, epipolarization microscopy and dispersive X-ray spectrometry, we have shown that matrix-associated PAI-1 is synthesized by spreading human mesangial cells, as indicated by the time-dependent accumulation of PAI-1 and the inhibitory effect of cycloheximide. Furthermore, by in situ hybridization, PAI-1 mRNA was detected in cultured mesangial cells. t-PA is present inside the cells, or at the cell surface, but is never associated with the extracellular matrix. Exogenous t-PA can remove matrix-associated PAI-1 without affecting cell adhesion. A similar effect was obtained by addition of urokinase-type plasminogen activator (u-PA) but not with fibrinolysis unrelated enzymes. In conclusion, PAI-1 is synthesized by human cultured mesangial cells and is deposited in the extracellular matrix by nonconfluent cells, whereas less PAI-1 is seen between confluent cells. This can explain the absence of detectable PAI-1 in normal human kidney biopsies. t-PA released by mesangial cells can bind and detach matrix PAI-1.     

Association between platelet activation and fibrinolysis in acute stroke patients

We aimed to evaluate platelet activation and fibrinolyis in acute atherosclerotic ischemic stroke patients to clarify the relationship between them. Plasma P-selectin antigen, tissue plasminogen activator (tPA) antigen and activity, and plasminogen activator inhibitor-1 (PAI-1) activity were determined in 60 acute atherosclerotic stroke patients and matched control subjects. All patients were examined within 72 h after stroke onset. The levels of P-selectin, tPA antigen, and PAI-1 activity were all significantly higher in stroke patients compared with controls (all p < 0.0001); the level of tPA activity was significantly lower in patients than that in controls (p < 0.0001). These markers did not change much at different time points within 72 h. In stroke group, P-selectin concentration was highly correlated to PAI-1 activity (r = 0.8433, p < 0.001), but not to tPA antigen (r = -0.1752, p > 0.05), and tPA activity (r = 0.2465, p>0.05), which was further confirmed in the multiple linear regression analysis (F = 47.052, p < 0.0001). Our results indicate increased platelet activation and decreased fibrinolysis in patients with acute atherosclerotic ischemic stroke. Increased platelet activation may be correlated with decreased fibrinolysis.     

Acute psychological stress decreases plasma tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 (tPA/PAI-1) complexes in cardiac patients

Tissue plasminogen activator (tPA) promotes fibrinolysis, and impaired fibrinolysis is associated with atherosclerosis and thrombosis. Plasminogen activator inhibitor-1 (PAI-1) inhibits t-PA expression. The effects of acute laboratory stressors on tPA and tPA/PAI-1 complexes were assessed in a sample of 11 cardiac patients. Participants were randomly assigned to either a stress or relaxation condition at time 1, and the alternative condition at time 2. Blood samples were taken before (pre) and after (post) each session and participants completed a battery of psychological questionnaires. Two-way repeated-measures analysis of variance revealed a statistically significant decrease in tPA (P = 0.01) and tPA-PAI-1 complexes (P = 0.04) during the mental stress condition. Anger-in had a strong relationship to decreases in tPA/PAI-1 levels in the stress condition (r = 0.68, P < 0.05). Relaxation had no significant effect on tPA and tPA/PAI-1 levels. These data suggest that decreased fibrinolysis mediates the relationship between mental stress and atherosclerosis.     

Tissue plasminogen activator and plasminogen activator inhibitor type 1 gene polymorphism in patients with gastric ulcer complicated with bleeding

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) may be involved in the pathogenesis of peptic ulcers through suppression of fibrinolysis. This study was designed to investigate associations of t-PA and PAI-1 genes with clinical features of the patients with bleeding gastric ulcers. Eighty-four patients with peptic ulcers and 100 controls were studied between January 1998 and April 2000. We used polymerase chain reaction and endonuclease digestion to genotype for 4G/5G polymorphism in the promoter region of the PAI-1 gene and the Alurepeat insertion/deletion (I/D) polymorphism in intron h of the t-PA gene. Various clinical features, including lesion site, bleeding event, recurrence of ulcer, and rebleeding, were assessed using a multiple logistic regression model. The genotype distributions of both the t-PA and PAI-1 genes did not differ between the patient and control groups. The occurrence of the I/D or D/D genotype of t-PA was significantly higher in cases of duodenal ulcer (adjusted OR=4.39, 95% CI=1.12-17.21). When a dominant effect (i.e., 4G/4G or 4G/5G versus 5G/5G) of the 4G allele was assumed, the PAI-1 4G/4G genotype was independently associated with rebleeding after hemostasis (adjusted OR=5.07, 95% CI=1.03-24.87). Our data suggest that t-PA gene polymorphism is associated with duodenal ulcers, and that the PAI-1 gene may be a risk factor leading to recurrent bleeding after initial hemostasis.     

Increase of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma after thrombolytic therapy of patients with myocardial infarction. A randomised,placebo-controlled study

Based on recent studies we hypothesised that the marked generation of thrombin in patients who undergo coronary thrombolysis was associated with substantial deviations of endogenous tissue-type plasminogen activator (t-PA) and the plasminogen activator inhibitor type 1 (PAI-1) in plasma.In the present placebo-controlled study we observe in 20 patients treated with recombinant t-PA (rt-PA) a marked increase (p<0.001) of antigen concentrations in plasma of endogenous t-PA and PAI-1 during the first 12h after initiation of treatment. The concentrations of endogenous t-PA and PAI-1 in plasma correlated significantly (p<0.05) with an estimate of generated thrombin in vivo, determined as plasma concentrations of thrombin-antithrombin III complexes. We conclude that the generation of coagulant activity following coronary thrombolysis is associated with an increased synthesis and/or release of endogenous t-PA and PAI-1, which suggests that the procoagulant condition involves an altered functional state of the vascular endothelium.     

Low levels of plasminogen activator inhibitor type 1 in patients with inflammatory bowel disease

Recent investigations suggest that microthrombi formation in bowel capillaries could be a determinant factor in inflammatory bowel disease (IBD) pathogenesis. To evaluate the implication of fibrinolysis in these thrombotic events, we analysed plasmatic values of physiologic activators, effectors and inhibitors of fibrinolysis. In a sample of 112 IBD patients we found decreased plasminogen activator inhibitor type 1 (PAI-1:Ag) levels, a finding which has not been reported to date: 8.8±1.1 ng/mL (mean±SEM) versus 17.8±1.1 ng/mL in controls (p<0.0001). Urokinase-type plasminogen activator (u-PA:Ag) from patients with inflammatory activity was decreased: 0.41±0.03 ng/mL in active disease versus 0.52±0.02 ng/mL in inactive disease (p=0.01) and the same applied to patients with Crohn's disease (CD) (0.38±0.03 ng/mL) with respect to ulcerative colitis (UC) patients (0.52±0.025 ng/mL), p=0.001. Levels of plasminogen, alpha 2 antiplasmin and tissue-type plasminogen activator (t-PA:Ag) showed no differences with respect to the controls. With the exception of u-PA:Ag, there were no differences between UC and CD. These results demonstrate plasmatic disturbances in the flbrinolytic system of IBD patients.     

Neutralization of plasminogen activator inhibitor-1 (PAI-1) by activated protein C is species-dependent

The interaction of bovine and human activated protein C (APC) with type-1 plasminogen activator inhibitor (PAI-1) was studied in a cell-free system. Human plasma and a preparation of PAI-1 obtained from human endothelial cell cultures were used as sources of PAI-1. Bovine APC was able to neutralize PAI-1 inhibitory activity present in both sources in a dose-dependent manner; the concentration of bovine APC required to produce 50% (C₅₀) neutralization of endothelial PAI-1 (0.5nM) was 4 μg/ml (64nM). Moreover, when complexes between tissue plasminogen activator (t-PA, 60ng/ml, 0.84nM) and PAI-1(18.8ng/ml, 0.35nM) were incubated with bovine APC, the amount of such complexes decreased as a function of the concentration of added APC (C₅₀ = 2 μ/ml, 32 nM), and a concomitant increase in the amount of residual t-PA activity was observed. This effect was due to the formation of APC⊎PAI-1 complexes as detected by immunoblotting with monoclonal antibodies directed against PAI-1. By this mechanism bovine APC prevented the initial reaction between PAI-1 and t-PA and interfered with the stability of complexes between t-PA and PAI-1. The latter observation suggests that complexes between t-PA and PAI-1 may dissociate in the presence of bovine APC. In contrast with these findings, when the experiments were performed in an entirely human homologous cell-free system, human APC did not form a complex with PAI-1 and no effect either on PAI-1 or on the stability of preformed t-PA ⊎ PAI-1 complexes was observed. The results indicate that the neutralization of PAI-1 by APC is a phenomenon induced by interspecies molecular interactions.     

On lipoprotein(a) and the coagulation/fibrinolysis balance in the acute phase of deep venous thrombosis

In vitro studies have suggested that lipoprotein(a) (Lp(a)), an important risk factor for the development of atherosclerotic cardiovascular and cerebrovascular disease, might interfere with fibrinolysis. We studied the correlations in vivo between Lp(a) and various coagulation and fibrinolysis factors in acute deep venous thrombosis, a state associated with an activated coagulation system and increased reactive fibrinolysis. In 31 patients with established acute deep venous thrombosis of the lower limb, coagulation parameters (fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (D-dimers, tissue plasminogen activator antigen, plasminogen) were studied in relation to Lp(a) concentrations. Elevated thrombin-antithrombin III and fibrin monomer levels were found together with enhanced D-dimers and tissue plasminogen activator concentrations, signs of an activated coagulation system and of increased reactive fibrinolysis. Significant correlations were obtained for fibrin monomers with thrombin-antithrombin III and D-dimers (r=0.56; p=0.002 and r=0.68; p=0.0002 respectively), between fibrin monomers and plasminogen (r=0.38; p=0.03) and for thrombin-antithrombin III with tissue plasminogen activator antigen (r=0.64; p=0.006). These data are indicative of a normally functioning coagulation/fibrinolysis axis in acute deep venous thrombosis. No correlation between Lp(a) concentrations and coagulation or fibrinolysis parameters was found in these patients with acute deep venous thrombosis, which suggests that variations in Lp(a) concentrations are not accompanied by parallel changes in coagulation and fibrinolysis parameters.     

Hyperfibrinolysis in hepatosplenic schistosomiasis.

AIM: To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis. METHODS: The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out. RESULTS: The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature. CONCLUSION: These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.     

PTCA前后t-PA及PAI-I的动态变化及意义

目的观察急性冠脉综合征（ACS）患者冠脉成形术（PTCA）前后血浆组织型纤溶酶原激活物（t-PA）及纤溶酶原激活抑制剂（PAI-I）的动态变化。探讨PTCA对机体纤溶功能的影响。方法采用发光底物法对36例ACS患者在PTCA前及后4、12、24、48、72h时间段测定血浆中t-PA和PAI-I的活性。结果PTCA术后4、12、24、48、72ht-PA活性明显降低，但术后24h开始t-PA活性呈逐渐升高趋势。PTCA术后4、12、48、72hPAI-I活性明显升高，但术后24h开始PAI-I活性呈逐渐下降趋势。结论ACS患者PTCA后存在着明显的纤溶功能低下．纤溶水平的高低与PTCA治疗效果及再梗塞发生有关。提示机体纤溶功能影响PTCA的手术效果。     

Acute psychological stress decreases plasma tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 (tPA/PAI-1) complexes in cardiac patients

Tissue plasminogen activator (tPA) promotes fibrinolysis, and impaired fibrinolysis is associated with atherosclerosis and thrombosis. Plasminogen activator inhibitor-1 (PAI-1) inhibits t-PA expression. The effects of acute laboratory stressors on tPA and tPA/PAI-1 complexes were assessed in a sample of 11 cardiac patients. Participants were randomly assigned to either a stress or relaxation condition at time 1, and the alternative condition at time 2. Blood samples were taken before (pre) and after (post) each session and participants completed a battery of psychological questionnaires. Two-way repeated-measures analysis of variance revealed a statistically significant decrease in tPA (P=0.01) and tPA-PAI-1 complexes (P=0.04) during the mental stress condition. Anger-in had a strong relationship to decreases in tPA/PAI-1 levels in the stress condition (r=0.68, P?<?0.05). Relaxation had no significant effect on tPA and tPA/PAI-1 levels. These data suggest that decreased fibrinolysis mediates the relationship between mental stress and atherosclerosis.     

Fibrinolysis after delivery: caesarean section versus vaginal delivery

Caesarean section is associated with higher risk of thromboembolism than normal vaginal delivery. In order to elucidate if altered fibrinolysis contributes to this increased risk, 15 women who delivered by Caesarean section were observed in the 37th to 40th week of pregnancy, 1 h, 3 and 10 days after delivery and compared to 15 women who delivered vaginally. Before delivery no differences in fibrinolytic variables were observed between the two groups. The immediate post-delivery period was associated with significant (all p<0.05) and similar increases in tissue-type plasminogen activator (t-PA) activity (149 vs 129%, all figures: Caesarean section vs vaginal delivery) and t-PA antigen (46 vs 75%) and significant (all p<0.05) decreases in plasminogen activator inhibitor (PAI) activity (66 vs 69%) and PAI-1 antigen (74 vs 82%) in both groups. Only euglobulin activity was less enhanced (60 vs 159% increase, p<0.05). Three days after delivery all variables, except PAI activity, decreased significantly (all p<0.05) compared to values 1 h after delivery (t-PA activity: 37 vs 41%; t-PA antigen: 43 vs 51%; PAI-1 antigen: 80 vs 58%) and similarly in both groups. From the 3rd to the 10th day euglobulin activity, t-PA activity and t-PA antigen slightly increased. The venous occlusion test, which was performed before delivery, 3 and 10 days after delivery revealed no significant differences in fibrinolytic responses to such stimulation between the two groups investigated. It was concluded that changes in t-PA and PAI-1 observed after Caesarean section are not significantly different from those observed after normal vaginal delivery and therefore presumably do not contribute to increased risk of thromboembolism after Caesarean section.     

慢性肾脏疾病血清和尿液纤溶活性物质的改变及临床意义

目的探讨慢性肾脏疾病血清和尿液纤溶活性物质的改变及其临床意义。方法选择38例慢性肾小球肾炎(CGN),28例肾病综合征(NS),36例非透析治疗的慢性肾功能不全(CRF)和20例正常对照作为研究对象,应用ELISA法检测血清和尿液中组织型纤溶酶原激活剂(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)的浓度,同时分析尿中t-PA和PAI-1的水平与血t-PA、PAI-1、血肌酐和24h尿蛋白总量之间相关性。结果慢性肾脏疾病出现血清t-PA、PAI-1升高,尿液t-PA、PAI-1降低,其中尿液t-PA、PAI-1的改变独立于血清,不受血肌酐和24h尿蛋白定量的影响。结论慢性肾脏疾病患者存在纤溶活性物质的异常,其中尿液纤溶活性物质的改变可反应肾脏内皮细胞损伤。