慢性心力衰竭患者血浆组织型纤溶酶原激活物和纤溶酶原激活物抑制物-1含量变化及其临床意义

目的　研究慢性心力衰竭 (CHF)患者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 1(PAI 1)含量的变化及其临床意义。方法　用酶联免疫吸附法 (ELISA)检测 6 0例CHF患者 (CHF组 )和 2 0例健康体检者 (正常对照组 )血浆t PA及PAI 1抗原含量。结果　CHF组血浆t PA和PAI 1平均含量都明显高于对照组 (P<0 .0 1)。CHF患者血浆PAI 1含量增高随心功能恶化而愈加明显。结论　CHF患者纤溶功能明显下降 ,可用血浆t PA、PAI 1含量作为判断病情的参考指标之一。     

尿激酶型纤溶酶原激活物受体研究进展

尿激酶型纤溶酶原激活物受体(u-PAR)是细胞表面的一个多功能的受体,它在肿瘤细胞侵润、血管新生等一些病的生理过程中起重要的作用。本文就近年有关的研究进展进行综述。     

尿激酶型纤溶酶原激活物受体研究进展

尿激酶型纤溶酶原激活物受体(u—PAR)是细胞表面的一个多功能的受体，它在肿瘤细胞侵润、血管新生等一些病的生理过程中起重要的作用。本文就近年有关的研究进展进行综述。     

尿激酶型纤溶酶原激活物及其受体检测的应用

至今人们已经充分认识到血液凝固和纤溶并非单纯的止血血栓及其保持血液循环通畅的功能.     

尿激酶型纤溶酶原激活物及其受体检测的应用

至今人们已经充分认识到血液凝固和纤溶并非单纯的止血血栓及其保持血液循环通畅的功能。就病理生理学意义而言 ,它除了血液学本身外 ,血液凝固和纤溶与组织修复、细胞生理 (增殖、运动、连接、形态变化和分化 )、分泌管道通畅、生殖生育过程、巨噬细胞激活、血管新生、炎性反应、新生物的形成等有关。而在众多的病理生理反应中 ,血液凝固和纤溶过程又大多是疾病发病机理的共同应答反应或反应环节 ,往往成为疾病发生发展的契机或促发因素。在参与的这些常见的临床疾病中 ,近年对纤溶系统中的尿激酶型纤溶酶原激活物 (ｕｒｏｋｉｎａｓｅｔｙ…     

消化系疾病患者血浆尿激酶型纤溶酶原激活物及其受体检测

尿激酶型纤溶酶原激活物 (ｕ ＰＡ)与尿激酶型纤溶酶原激活物受体 (ｕ ＰＡＲ)是近年特别受关注的两个纤溶因子。现报道消化系疾病血浆ｕ ＰＡ、ｕ ＰＡＲ水平检测及其临床意义。对象和方法1　对象1.1　患者组 :消化系疾病组 117例 ,年龄 19～ 77岁 ,平均44 7岁 ,其中男 6 8例 ,女 49例 ,均为本院诊断明确的住院患者 ,诊断符合消化系疾病诊断标准。分为肿瘤组和非肿瘤组。肿瘤组 48例 ,包括胃癌 17例 ,胰癌 14例 ,肝癌 11例和大肠癌 6例 ;非肿瘤组 6 9例 ,包括肝硬化代偿期 8例 ,失代偿期 2 3例 ,浅表性胃炎和消化性溃疡 15例 ,急性胰腺炎 …     

急性胰腺炎患者尿激酶型纤溶酶原激活物及其受体的变化

目的探讨急性胰腺炎患者胰腺BalthazarCT分级、血钙和血镁的关系。方法采用病例对照研究设计,收集30例急性胰腺炎患者和30例正常对照组,采用ELISA法测定血浆uPA和uPAR。并对急性胰腺炎患者血浆uPA和uPAR与胰腺CT分级、血钙和血镁进行Pearson相关分析。结果急性胰腺炎患者血浆uPA和uPAR水平明显高于正常对照组。血浆uPA分别是(1304.70±497.43)ngL和(1033.93±276.60)ngL(t=2.606,P=0.012);血浆uPAR分别是(1184.67±398.69)ngL和(871.33±271.84)ngL(t=3.557,P=0.001)。经Pearson相关分析,急性胰腺炎患者血uPA与胰腺CT分级呈负相关(r=-0.435,P=0.016),与血钙无关(r=0.057,P=0.782),与血镁呈正相关(r=0.649,P=0.000)。血uPAR与胰腺CT分级无关(r=0.047,P=0.806),与血钙无关(r=0.104,P=0.615),与血镁呈正相关(r=0.420,P=0.021)。结论uPA及其受体uPAR与急性胰腺炎及其胰腺CT分级、血镁浓度有关。     

全身炎症反应综合征患者血浆尿激酶型纤溶酶原激活物及其特异性受体动态变化的研究

目的 观察全身炎症反应综合征(SIRS)患者血浆尿激酶型纤溶酶原激活物(uPA)及其特异性受体(uPAR)的动态变化以及对预后的影响.方法 采用前瞻性病例对照研究设计方法,将85例住院患者按SIRS诊断标准分为SIRS组(50例)和非SlRS组(35例);SIRS组再按病情分为单纯SIRS组(26例)和合并多器官功能障碍综合征(MODS)组(24例),按预后分为生存组(35例)和死亡组(15例);另选择同期30例健康体检者作为对照.非SIRS组于入院当日,SIRS组于发生SIRS后的1、3、5、7 d,健康对照组于体检时采集空腹静脉血2 ml,用双抗体夹心酶联免疫吸附法(ELISA)测定血浆uPA和uPAR含量,并分析SIRS患者血浆uPAR含量与急性生理学与慢性健康状况评分系统I(APACHE I)评分的相关性.结果 单纯SIRS组、合并MODS组患者血浆uPA和uPAR含量均较非SIRS组和健康对照组显著升高[uPA(μg/L):1.208±0.264、1.120±0.276比0.744±0.190、0.782±0.257;uPAR(μg/L):3.704±1.018、4.970±1.284比1.892±0.476、1.823±0.797,均P＜0.01],且合并MODS组uPAR含量明显高于单纯SIRS组(P＜0.01).与生存组比较,死亡组5 d、7 d血浆uPA含量(μg/L)明显升高(5 d:1.177±0.185比0.856±0.223,7 d:1.377±0.185比0.836±0.223,均P＜0.01),1、3、5、7 d血浆uPAR含量(μg/L)显著增高(1 d:5.301±1.410比3.888±1.015,3 d:4.017±0.898比2.994±0.638,5 d:5.032±1.238比2.536±1.017,7 d:5.232±1.238比3.536±1.017,均P＜0.01).SIRS患者血浆uPAR含量与APACHE I评分呈显著正相关(r=0.640,P＜0.O1).结论 SIRS患者存在凝血功能障碍,血浆uPA、uPAR含量显著增高,uPAR含量的升高提示预后不良.     

淋巴瘤患者血浆尿激酶型纤溶酶原激活物及其受体检测的临床意义

尿激酶型纤溶酶原激活物（u—PA）与尿激酶型纤溶酶原激活物受体（u—PAR）是近年特别关注的2个纤溶因子,他们除有纤溶作用外,还参与胞外基质降解、细胞修复和组织重塑等过程。这2个因子与白血病之间的关系有一些报道,但尚未见淋巴瘤方面的临床研究报告。为此,我们检测了淋巴瘤患者血浆u—PA和u—PAR,并对其含量变化的临床意义进行了探讨。     

uPA、uPAR、PAI-1血浆含量与卵巢恶性肿瘤的相关性研究

目的：探讨尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）和抑制剂（PAI-1）血浆含量与卵巢恶性肿瘤之间的关系。方法：收集52例卵巢恶性肿瘤患者血液标本,以30例健康人作对照,用ELISA法分别检测uPA、uPAR和PAI-1的含量。结果：uPA、uPAR在卵巢恶性肿瘤各期之间均有极显著性差异（P〈0．01）,PAI-1在卵巢恶性肿瘤FIGO Ⅰ～Ⅲ期的含量逐渐升高,但在FIG0Ⅳ期时显著下降（P〈0．05）。患者组uPA、uPAR、PAI-1均较对照组升高,差异极显著（P〈0．01）。结论uPA、uPAR在卵巢恶性肿瘤患者可作为预后的判断指标,PAI-1与卵巢恶性肿瘤的分期有一定的相关性。     

Clinical significance of urokinase-type plasminogen activator receptor (uPAR) expression in cancer

The involvement of the urokinase-type plasminogen activator (uPA) system in particular has been extensively studied in the pathogenesis of cancer. The molecular role of the uPA receptor (uPAR) is well characterized with its participation in cell migration and extracellular matrix (ECM) degradation. Over-expression of uPAR in cancer has been demonstrated in many studies and is considered an attractive target for anticancer agents. We and others have down-regulated uPAR expression in an attempt to inhibit cancer metastasis based on its molecular role. Uniquely, uPAR which is a glycosyl phosphatidylinositol anchored protein is not only bound to the cell surface but also has a soluble form, suPAR. There is now accumulated clinical and experimental evidence supporting the significant role of uPAR and its soluble counterpart in a number of solid cancers. The expression of uPAR can be associated with tumor cells or stromal cells or both. Differences observed in the expression of uPAR using immunohistochemistry (IHC) are likely explained by the use of different antibodies and techniques rather than true cellular differences and are reviewed here. This review summarizes the clinical relevance of uPAR and its soluble form in the prognosis and diagnosis of different cancers.     

Plasminogen activators and plasminogen activator inhibitor in malignant and non-malignant ascitic fluid

Ascitic fluid from tumour patients (hepatoma, gastric cancer, gallbladder cancer, colorectal cancer, ovarian cancer) and from non-malignant diseases (liver cirrhosis, congestive heart failure) were compared with respect to their content of determinants of the fibrinolytic system, tissue-type plasminogen activator antigen (t-PAag) and activity (t-PAact), urokinase-type plasminogen activator antigen (u-PA) and plasminogen activator inhibitor activity (PAI). Furthermore, SDS-polyacrylamide slab-gel electrophoresis (SDS-PAGE) was performed to evaluate molecular weight distribution of the detectable fibrinolytic parameters. In malignant ascites, PAI activity was three to four times higher, and increased complex formation of PAI with t-PA could be demonstrated, compared with non-malignant ascitic fluid. Tissue-type plasminogen activator antigen and activity showed a similar concentration in ascites of both study groups. Urokinase-type plasminogen activator antigen was detectable neither in ascites of malignant nor in ascites of non-malignant origin. It is concluded that t-PA is the physiological plasminogen activator in ascites and that increased PAI levels followed by increased complex formation between t-PA and PAI might reflect a reaction of the peritoneum.     

The regulation by fibrinogen and fibrin of tissue plasminogen activator kinetics and inhibition by plasminogen activator inhibitor 1

BACKGROUND: Tissue plasminogen activator (tPA) is unusual in the coagulation and fibrinolysis cascades in that it is produced as an active single-chain enzyme (sctPA) rather than a zymogen. Two chain tPA (tctPA) is produced by plasmin but there are conflicting reports in the literature on the behaviour of sc- and tctPA and little work on inhibition by the specific inhibitor plasminogen activator inhibitor-1 (PAI-1) under physiological conditions. OBJECTIVES: To perform a systematic study on the kinetics of sctPA and tctPA as plasminogen activators and targets for PAI-1. METHODS: Detailed kinetic studies were performed in solution and in the presence of template stimulators, fibrinogen and fibrin, including native fibrin and partially digested fibrin. Numerical simulation techniques were utilized to cope with the challenges of investigating kinetics of activation and inhibition in the presence of fibrin(ogen). RESULTS: Enzyme efficiency (k(cat)/K(m)) was higher for tctPA than sctPA in solution with chromogenic substrate (3-fold) and plasminogen (7-fold) but in the presence of templates, such as fibrinogen and native or cleaved fibrin, the difference disappeared. sctPA was more susceptible to PAI-1 in buffer solution and in the presence of fibrinogen; however, in the presence of fibrin, PAI-1 inhibited more slowly and there was no difference between sc and tctPA. CONCLUSIONS: Fibrinogen and fibrin modulate the activity of tPA differently in regard to their activation of plasminogen and inhibition by PAI-1. Fibrinogen and fibrin stimulate tPA activity against plasminogen but fibrin protects tPA from PAI-1 to promote fibrinolysis.     

血栓调节蛋白和组织纤溶酶原激活物-纤溶酶原激活物抑制剂-1复合物在热射病中的诊断价值

目的 探讨热射病时血栓调节蛋白(TM)和组织纤溶酶原激活物-纤溶酶原激活物抑制剂-1复合物(t-PAIC)的临床价值。方法 回顾性分析解放军联勤保障部队第九〇八医院重症医学科2016年6月至2022年9月收治的45例中暑患者，根据中暑严重程度分为热衰竭组(n=23)和热射病组(n=22)。收集患者入科2 h内的常规凝血项目和血栓弹力图(TEG)指标以及血栓标志物TM、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α₂纤溶酶抑制剂复合物(PIC)、t-PAIC,并进行统计学分析。结果 与热衰竭组患者TM[7.3(5.4,9.3)TU/mL]、TAT[2.6(1.5,7.2)ng/mL]、PIC[0.7(0.4,1.0)μg/mL]、t-PAIC[3.8(2.1,7.0)ng/mL]相比，热射病组患者TM[17.1(9.2,24.7)TU/mL]、TAT[23.4(10.4,44.3)ng/mL]、PIC[2.0(0.9,5.2)μg/mL]和t-PAIC[17.0(8.3,44.1)ng/mL]均升高(P<0.05)。单因素联合多因素Logistic回归分析显示，...     

消化道恶性肿瘤伴发皮肌炎病例分析

目的:探讨消化道恶性肿瘤合并皮肌炎的临床特征。方法:对6例消化道恶性肿瘤合并皮肌炎患者的临床资料进行回顾性分析。结果:皮肌炎可发生于消化道恶性肿瘤的任何时期,起病可为多种形式,二者密切相关,但以中线肌肉受累明显。病理改变以微血管病变为主。结论:皮肌炎与恶性肿瘤密切相关,消化道肿瘤伴发皮肌炎并非少见,皮肌炎确诊时间<1年及>50岁的中老年人应高度警惕恶性肿瘤的发生。     

纤溶酶原激活物抑制剂-1的研究进展

纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor 1,PAI-1)作为体内组织型纤溶酶原激活物(tissue-type plasminogen activator,t-PA)和尿激酶型纤溶酶原激活物(urokinase-type plasminogen activator,u-PA)的主要抑制剂,与动静脉血栓、出血和凝血异常、细胞迁移密切相关,进而引起缺血性脑卒中、冠心病、静脉血栓、肿瘤转移、出血、股骨头坏死、流产等一系列疾病的发生发展。同时,体内血浆PAI-1活性水平又受血脂、血糖等调节,进一步参与肥胖、糖尿病、高脂血症等疾病的进程,又影响着上述相关疾病的预后。     

Effect of pharmacologic plasminogen activator inhibitor-1 inhibition on cell motility and tumor angiogenesis

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is integrally involved in tumorigenesis by impacting on both proteolytic activity and cell migration during angiogenesis. OBJECTIVES: We hypothesized that an orally active small molecule inhibitor of PAI-1 (PAI-039; tiplaxtinin) could affect smooth muscle cell (SMC) attachment and migration in vitro on a vitronectin matrix, and exhibit antiangiogenic activity in vivo. METHODS: In vitro assays were used to assess the mechanism of inhibition of PAI-1 by PAI-039 using wild-type PAI-1 in the presence or absence of vitronectin and wild-type PAI-1 and specific PAI-1 mutants in SMC adhesion and migration assays. An in vivo tumor angiogenesis model was used to assess the effect of PAI-039 administration on neovascularization in a Matrigel implant. RESULTS: PAI-039 dose-dependently inhibited soluble, but not vitronectin-bound, PAI-1. Cell adhesion assays using PAI-1 mutants unable to bind vitronectin (PAI-1K) or inactivate proteases (PAI-1R) further suggested that PAI-039 inactivated PAI-1 by binding near its vitronectin domain. In a tumor angiogenesis model, PAI-039 treatment of wild-type mice dose-dependently decreased hemoglobin concentration and endothelial cell staining within the Matrigel implant, indicating reduced angiogenesis, but exhibited no in vivo efficacy in PAI-1 null mice. CONCLUSIONS: Administration of an orally active PAI-1 inhibitor prevented angiogenesis in a Matrigel implant. The lack of activity of PAI-039 against wild-type PAI-1 bound to vitronectin and PAI-1K suggests PAI-039 binding near the vitronectin-binding site. Our studies further substantiate a role for PAI-1 in cellular motility and tumor angiogenesis, and suggest for the first time that these effects can be modulated pharmacologically.     

高血压病患者血浆PAI-1、t-PA及t-PA/PAI-1水平的变化

目的通过对原发性高血压患者血浆纤溶酶原活化物抑制剂1(PAI-1)、组织型纤溶酶原活化物(t-PA)含量及t-PA/PAI-1比值的测定,了解高血压患者纤溶功能的情况。方法未用药物干预过的轻至中度原发性高血压患者(高血压组)64例,正常对照组42例,采用酶联免疫吸附双抗体夹心法测定两组血浆PAI-1、t-PA含量并计算t-PA/PAI-1。结果正常组PAI-1含量明显低于高血压组,(13.5±5.0)μg/L vs(53.0±22.6)μg/L(P<0.01);正常组t-PA/PAI-1明显高于高血压组,(0.83±0.52)μg/L vs(0.25±0.13)μg/L(P<0.01)。结论高血压患者的纤溶功能减退。