急性脑血管病患者血浆t-PA、PAI-1活性测定及意义

目的 研究急性脑血管病（脑梗死和脑出血）患者的血浆组织型纤溶酶原激活物（t-PA）和纤溶酶原激活物抑制物（PAI-1）的活性变化及临床意义.方法 采用酶联免疫吸附法测定67例急性脑梗死和53例脑出血患者的t-PA和PAI-1的活性,并计算P/t值,与50例正常对照组进行比较分析.结果 急性脑血管病组患者急性期（7d内）血浆t-PA及PAI-1活性均升高,与正常对照组比较有显著性差异（P＜0.05） 脑梗死组P/t值与正常对照组比较有显著性差异（P＜0.05） 脑出血组P/t值与正常对照组比较无显著性差异（P＞0.05）.结论 脑梗死和脑出血患者急性期血浆P/t改变不同 脑梗死患者急性期P/t降低,体内处于相对纤溶亢进状态 脑出血患者P/t变化不明显,体内凝血纤溶机制相对平衡P/t值可以更好地反映血液中的纤溶活性.     

Effects of a fucoidan on the activation of plasminogen by u-PA and t-PA

The effect of an anticoagulant fucoidan (C-I-H) from the brown seaweed Ecklonia kurome on the fibrinolytic system was studied in vitro using S-2251 as a substrate of plasmin. C-I-H enhanced the activation of Glu- and Lys-plasminogen by high molecular weight urokinase-type plasminogen activator (HMW u-PA) very effectively, but the activation by low molecular weight u-PA was hardly enhanced with C-I-H. C-I-H also potentiated moderately the activation by single- and two-chain tissue-type plasminogen activators (sct- and tct-PA). These effects of C-I-H were higher than those of heparin used. But C-I-H had no effect on the amidolytic activity of plasmin to S-2251. These results indicate that C-I-H promotes the generation of plasmin in the plasminogen activation by HMW u-PA and t-PA, but not the activity of generated plasmin. Kinetic analyses suggest that C-I-H enhances the HMW u-PA-mediated plasminogen activation by increasing the affinity of the activator for Glu- and Lys-plasminogen and by increasing the molecular activity of the activator. On the other hand, C-I-H had no effect on the affinity of tct-PA for both plasminogens. The catalytic efficiencies of HMW u-PA and tct-PA for the activation of both plasminogens were increased with C-I-H about 8- and 2-fold, respectively. The present results suggest that C-I-H has the fibrinolytic activity by stimulating the plasminogen activation by HMW u-PA and t-PA. The mechanism of the enhancement effect of C-I-H on the activation is presumed to be that C-I-H binds to plasminogen, thereby inducing a structural change of plasminogen susceptible to the action of plasminogen activators.     

水蛭提取液对实验性脑内血肿周围组织tPA、PAI-1的影响

目的探讨水蛭提取液对实验性脑内血肿周围组织组织型纤溶酶原激活物（tPA）、纤溶酶原激活剂抑制物1（PAI-1）的影响。方法采用成组设计的随机对照研究。用定量胶原酶注入大鼠尾状核来建立脑出血模型．酶联免疫吸附法、发色府物法检测血肿周围脑组织生化指标（tPA、PAI-1含量与活性）变化，RT-PCR法观察鼠脑血肿周围脑组织tPA与PAI-1 mRNA的表达，免疫组化法观察鼠脑血肿周围脑组织tPA蛋白的表达。结果水蛭提取液治疗组较生理盐水对照组能增加血肿周围脑组织tPA含量、提高其活性，促进血肿周围脑组织tPA mRNA表达，增强tPA免疫表达．而不影响PAI-1含量与活性或mRNA表达。结论水蛭提取液促进实验性脑内血肿吸收的机制可能为通过对tPA的转录、翻译及合成蛋白的加工修饰来激活内源性纤溶系统，对PAI-1无影响。     

Association of tissue plasminogen activator and plasminogen activator inhibitor polymorphism with myocardial infarction: A meta-analysis

Introduction

To investigate whether t-PA Alu repeat insertion/deletion (I/D) and PAI-1 4 G/5 G genetic variations are associated with the risk of MI.

Methods

We conducted a meta-analysis to assess the association between the t-PA I/D and PAI-1 4 G/5 G polymorphisms and risk of MI. We also performed subgroup analyses based on ethnicity (Caucasian, Asian, and African), gender and age. Forty one eligible studies including 12,461 cases and 14,993 controls were identified to evaluate the impact of PAI-1 4 G/5 G polymorphism on MI. Seven studies investigated the relationship between t-PA I/D and MI.

Results

This meta-analysis revealed that the PAI-1 4 G allele (4 G/4 G and 4 G/5 G genotype) was associated with an increased risk of MI compared with the 5 G allele in the overall population (OR = 1.094, 95% CI = 1.021 - 1.172, p = 0.011). The relative risks of MI for 4 G/4 G genotype was increased when compared to 5 G/5 G genotype and 5 G allele, with odds ratio at 1.157 (95% CI 1.015 - 1.320, p = 0.029) and 1.126 (95% CI = 1.015 - 1.249, p = 0.025). However, the results show that the 4 G/5 G polymorphism risk for MI was not associated with ethnicity stratification as Caucasian, Asian or African population. No substantial differences in the genotype distributions were observed in the MI group and control group along the lines of gender and age. After multivariable analysis t-PA I/D polymorphism showed no consistent association with MI.

Conclusions

This study suggests that the 4 G/5 G polymorphism of PAI-1 may be a risk factor for MI in overall populations.     

急性脑梗死患者血浆纤溶酶原激活物及其抑制剂-1水平的动态变化及其与梗死面积的关系

目的 探讨急性脑梗死患者血浆组织型纤溶酶原激活物(t-PA)及其抑制剂-1(PAI-1)水平的动态变化及其与梗死面积的关系.方法 急性脑梗死患者100例,其中大面积脑梗死22例、小面积脑梗死36例、腔隙性脑梗死42例,采用发色底物显色法检测脑梗死患者病后24 h、2 d、14 d、21 d的血浆t-PA、PAI-1水平,与正常对照组比较;并比较不同面积脑梗死患者血桨t-PA、PAI-1水平.结果 与正常对照组比较,急性脑梗死患者病后24 h、2 d、14 d血浆t-PA水平显著降低,血浆PAI-1水平明显升高(均P＜0.01);病后21 d两者与正常对照组差异无统计学意义(均P＞0.05);大面积脑梗死患者t-PA水平明显低于小面积和腔隙性脑梗死患者,小面积脑梗死患者又明显低于腔隙性脑梗死患者(均P＜0.01);不同面积脑梗死组之间PAI-1水平未见明显差异(均P＞0.05).结论 脑梗死患者急性期血浆t-PA水平降低及PAI水平升高;脑梗死面积越大的患者血浆t-PA水平降低程度越明显,而血浆PAI-1水平与梗死面积无关.     

Circulating platelet-derived microparticles and endothelium-derived microparticles may be a potential cause of microthrombosis in patients with osteonecrosis of the femoral head

Introduction

To test the hypothesis that the platelet microparticle (PMP) and endothelial microparticle (EMP) may contribute to the hypercoagulability associated with microvascular thrombosis in patients with nontraumatc osteonecrosis of the femoral head (ONFH).

Materials and methods

The study comprised 46 patients who had been diagnosed with ONFH and 20 control subjects. The plasma was ultracentrifuged, and then PMPs and EMPs were examined by the flow cytometry. The thrombotic and fibrinolytic disorders were investigated.

Results

The numbers of PMPs expressing P-selectin and CD42a and EMPs expressing E-selectin and CD31 in the ONFH patients were significantly higher than those in the controls (P < 0.001). The number of MPs was correlated with the level of the serum C-reactive protein (CRP) (r = 0.661, P < 0.001), but there was a poor correlation between the MPs counts and the risk factors for ONFH (P > 0.05). The mean levels PAI-1, F1 + 2, and TAT were higher in the patients with ONFH than in the controls (P < 0.05).

Conclusions

The elevated numbers of PMPs and EMPs may contribute to hypercoagulability in the ONFH patients. This may provide important pathophysiological insights into the hypercoagulability associated with nontraumatic ONFH and have implications for pharmacological prevention and treatment of ONFH.     

In vitro effects of detergent sclerosants on fibrinolytic enzymes and inhibitors

Objective

To investigate the effects of Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on fibrinolytic mechanisms.

Materials and methods

Measurements were done with serial dilutions of sclerosants in whole blood (WB), platelet rich (PRP) and platelet poor plasma (PPP). Control experiments were done in 5% bovine serum albumin (BSA), spiked with the enzyme/inhibitor. Plasminogen was measured with a chromogenic assay. Alpha-2-antiplasmin (AP) activity, plasmin-alpha-2-antiplasmin (PAP) complexes, plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator (t-PA) total antigen, t-PA activity, t-PA/PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI) antigen and activated TAFI (TAFIa) were measured by ELISA.

Results

At high concentrations (> 0.3%), STS destroyed plasminogen, PAI-1, t-PA/PAI-1 complexes and total t-PA antigen but increased t-PA activity. At low concentrations (< 0.3%), both agents reduced PAP complexes while increasing AP activity. Low concentration STS increased PAI-1 activity, t-PA/PAI-1 complexes, TAFI and TAFIa. Low concentration POL mildly increased the total t-PA antigen and TAFI.

Conclusion

At low concentrations, both agents demonstrated a prothrombotic, antifibrinolytic (increase in PAI-1, total t-PA antigen, AP, TAFI and TAFIa) activity. At high concentrations, STS demonstrated non-prothrombotic (destruction of PAI-1, t-PA/PAI-1 complexes), antifibrinolytic (destruction of plasminogen, increase in AP) activity while POL had minimal effect.     

Effect of Zhutan Tongluo Tang on fibrinolytic activity following intracerebral hemorrhage in rats

The neuroprotective effect of Zhutan Tongluo Tang is associated with the activities of the fibrinolytic system. Thus the present study was designed to investigate therapeutic effects of Zhutan Tongluo Tang on intracerebral hemorrhage in rats, induced by injecting collagenase into one side of the caudate nucleus. Fibrinolytic indices including tissue plasminogen activator, plasminogen activator inhibitor-1 and D-Dimer were determined. The results obtained demonstrated that Zhutan Tongluo Tang treatment could...     

Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.