癌症患者血浆PAI-1浓度变化

目的测定多种恶性肿瘤患者血浆中纤溶酶原激活物抑制剂1(Plasminogen activator inhibitor-1,PAI-1)浓度变化情况,探讨PAI-1血浆含量变化作为恶性肿瘤诊断中的作用。方法收集乳腺癌、肺癌、喉癌血液标本各40例,并以正常人血液标本作对照,用ELISA法检测肿瘤患者及正常对照组血浆中PAI-1的含量,并比较其差异。结果与正常对照组(9.84±4.66 ng/ml)相比,乳腺癌(21.49±10.54 ng/ml),肺癌(15.10±8.55 ng/ml),喉癌(14.03±7.14 ng/ml)患者血浆中PAI-1含量均明显升高,其中乳腺癌组与正常组相比差异极为显著(P0.01)。结论血浆中PAI-1的浓度升高可作为肿瘤诊断辅助指标,PAI-1可作为肿瘤治疗潜在靶位。     

老年急性脑梗死病人凝血系统变化的临床研究

目的　探讨血浆组织型纤溶酶原激活物 (t-PA)及其抑制物 (PAI- 1)和血小板a颗粒膜蛋白 - 14 0 (CD6 2p)在老年人急性脑梗死发病中的临床价值。方法　对 5 6例急性脑梗死病人采用ELISA法检测t-PA和PAI- 1活性 ,计算t-PA/PAI- 1比值 ;流氏细胞仪测定CD6 2p ,并与对照组进行比较。结果　与对照组相比 ,急性脑梗死发病急性期 (<1周 )血浆t-PA水平和t-PA/PAI- 1比值明显下降 (P <0 0 1) ,血浆CD6 2p、PAI- 1明显增高 (P <0 0 1)。 3周后 ,急性脑梗死组血浆t-PA水平和t-PA/PAI- 1比值上升 ,与急性期相比P <0 0 5 ;血浆CD6 2p、PAI- 1下降 (P <0 0 5 )。结论　血小板活化、纤溶系统失衡参与了老年人脑梗死的发病发展过程 ,CD6 2p、PAI- 1和t-PA/PAI- 1比值作为老年人脑梗死进展的预警指标具有一定的临床参考价值。     

脑梗死患者血浆炎症因子、纤溶活性的变化及对神经功能的影响

目的通过观察急性脑梗死患者血浆中的Ⅷ因子相关抗原(vWF)、P-选择素(P-Selectin)、白细胞介素-6(IL-6)、组织型纤溶酶原激活物(t-PA)及快速抑制物(PAI-1)的变化规律,探讨炎症因子及纤溶活性在脑梗死发生、发展、转归过程中的作用。方法采用酶联免疫吸附(ELISA)及发色底物法对40例急性脑梗死患者发病后6,12,24及72h血浆vWF,P-selectin,IL-6,t-PA及PAI-1活性进行动态测查。并与32例自愿者健康对照组进行比较。结果在急性脑梗死患者发病24h内,vWF(147.4±26.2)μg/ml、P-selectin(21±4)ng/ml、IL-6(114.5±1.5)μg/ml、PAI-1(0.79±0.24)au/ml活性明显增高,t-PA活性(0.24±0.15)iu/ml明显降低,与对照组比较差异有显著性意义(P<0.05);随时间推移vWF(118.6±24.4)μg/ml、P-selectin(14±3)ng/ml、IL-6(108.7±4.4)μg/ml、PAI-1(0.56±0.20)au/ml活性有所降低,而t-PA活性(0.43±0.11)iu/ml升高,但与正常对照组相比仍有差异(P<0.05)。结论(1)急性脑梗死患者早期存在内皮细胞损伤;(2)炎症因子参与脑部缺血性损害;(3)纤溶活性下降,说明t-PA及PAI-1参与了血栓形成的病理过程。     

tPA和PAI-1活性与自然流产的相关性

【目的】探讨组织型纤溶酶原激活剂（tPA）和纤溶酶原激活剂抑制剂-1（PAI-1）活性与自然流产的相关性。【方法】选择2003年10月至2004年3月中南大学湘雅二医院门诊有自然流产史患者71例（非孕50例．孕妇21侧）和对照组41例（非孕20侧,孕妇21例）进行研究,运用发色底物法测定血浆tPA和PAI-1活性。【结果】非孕有自然流产史的研究组tPA活性比对照组低（t=2．226,P=0．029〈0．05）,早孕研究组tPA活性比对照组低（t=2．166,P=0．036〈0．05）,差别均有统计学意义;研究组中,tPA活性早孕高于非孕（t=-2．937,P=0．005）,PAI-1活性早孕低于非孕（t=2．428,P=0．018）;在对照组中,tPA活性早孕也高于非孕（t=2．597,P=0．013）,PAI-1活性早孕也低于非孕者（t=2．653,P=0．012）。差别均有统计学意义。【结论】妊娠后tPA活性增高和PAI-1活性下降。有自然流产史者在非孕状态时tPA活性明显下降,且妊娠后呈低增长水平。tPA活性下降与引起自然流产的发病机制有关。     

消化道肿瘤患者血浆尿激酶型纤溶酶原激活物系统的变化及其意义

目的观察消化道恶性肿瘤患者血浆尿激酶型纤溶酶原激活物(u-PA)及其特异性受体(u-PAR)和纤溶酶原激活物抑制物-1(PAI-1)含量的变化及其与肿瘤转移和预后的关系.方法用酶联免疫吸附测定(ELISA)法测定43例消化道恶性肿瘤患者和21例正常人血浆中u-PA、u-PAR和PAI-1含量.结果食管癌、胃癌和结肠癌患者的血浆u-PA、u-PAR和PAI-1含量均显著升高(P<0.05～0.01);肿瘤组中,中、晚期组u-PA显著高于早期组(P＜0.05),已转移组u-PA、u-PAR和PAI-1较未转移组显著升高(P<0.05～0.01).结论消化道恶性肿瘤患者血浆中u-PA、u-PAR和PAI-1含量不同程度升高,并与肿瘤转移和预后相关.     

纤溶酶原激活物抑制物-1基因多态性及其血浆水平在急性肺动脉血栓栓塞中的作用

目的 探讨纤溶酶原激活物抑制物-1(plasminogen activator inhibitor-1,PAI-1)基因4G/5G多态性、PAI-1和组织型纤溶酶原激活物(tissue plasminogen activator,t-PA)血浆水平在急性肺动脉血栓栓塞(acute pulmonary thromboembolism,APTE)中的作用.方法 选择52例急性肺栓塞患者(分为2组:26例有环境诱因,26例无环境诱因)和57例正常对照者,聚合酶链反应-限制性片段长度多态性法检测PAI-1基因型,酶联免疫吸附试验测定血浆PAI-1和t-PA水平.结果 (1)无环境诱因组4G/4G基因型显著高于有环境诱因组和正常对照组(P=0.034),而有环境诱因组与正常对照组比较差异无统计学意义.(2)无明确环境诱因组t-PA明显降低,PAI-1明显升高与有环境诱因组、正常对照组比较差异有统计学意义(P＜0.05),而有环境诱因组与正常对照组比较无显著差异.(3)在三组中,无论何种基因型,无环境诱因组的PAI-1血浆水平均最高.在4G/4G基因型和4G/5G基因型中,无环境诱因组与正常对照组、有环境诱因组的差异有统计学意义(P＜0.05).4G等位基因与PAI-1血浆水平具有相关性.结论 纤溶酶原激活物抑制物-1基因多态性与急性肺栓塞有关,4G/4G基因型显著增加无肺栓塞环境诱因个体肺栓塞危险.急性肺栓塞无环境诱因患者存在明显的低纤溶状态.     

电针对急性脑梗死大鼠血浆t-PA和PAI-1含量的影响

目的:研究电针对急性脑梗死大鼠血浆组织型纤溶酶原激活物(t-PA)及纤溶酶原激活物抑制物-1(PAI-1)含量的影响。方法:40只SD大鼠随机分为正常组、假手术组、模型组及电针组各10只,模型组及电针组大鼠制成脑梗死模型;假手术组手术步骤同前2组,但不线栓;正常组不作任何处理。造模成功后,4组大鼠均同步喂养,电针组大鼠于造模成功后即刻给予电针百会、水沟穴,每天1次,30min。治疗5d后,4组大鼠均采用ELISA法检测血浆t-PA及PAI-1含量。结果:与正常组及假手术组比较,模型组及电针组大鼠血浆t-PA、PAI-1含量均显著升高(P<0.01),但电针组低于模型组(P<0.05,0.01)。结论:电针能显著降低急性脑梗死大鼠血浆t-PA、PAI-1含量,调节机体纤溶系统活性,改善梗死区域的血液循环,促进功能恢复。     

缺血性脑卒中患者血纤溶活性变化规律的研究

目的 研究脑梗死组和非脑梗死组患者急性期,亚急性期和恢复期组织型纤溶酶原激活物（tPA）,纤溶酶原激活物抑制物-1（PAI-1）的变化规律.方法 135例脑梗死组患者于发病96h内,病后14d、3月、6月、9月分别采血,77例非脑梗死组患者先采血一次,然后分别在第一次采血后14d、3月、6月、9月采血.结果 脑梗死急性期tPA含量明显升高,PAI-1的含量明显升高.恢复期脑梗死即发病后3月,6月,9月tPA的含量比急性期明显降低,且脑梗死后时间越长tPA含量越低,恢复期脑梗死PAI-1的含量比急性期明显降低.结论 在缺血性卒中的患者,高tPA含量提示纤溶活性的降低.高PAI-1代表纤溶抑制增强.     

中老年体检者血浆纤溶相关因子与颈动脉内膜及中层厚度和颈动脉粥样硬化的关系

目的：探讨中老年教职工体检者血浆血管性假血友病因子(von Willebrand factor，vWF)以及血管性假血友病因子前肽(propeptide of von Willebrand factor．vWFpp)与组织纤溶酶原激活物(tissue-type plasminogen activator，tPA)、纤溶酶原激活抑制物-1(plasminogen activator inhibitor-1，PAI-1)浓度、颈动脉血管内膜-中层的厚度(carotid arterial intima media thickness，IMT)和血流速度、颈动脉粥样硬化病变的关系。方法：随机选择28例(年龄40～60岁)无心、脑血管意外病史的体检者，按年龄分为高年龄组(≥50岁)、低年龄组(&;lt;50岁)。分别进行血浆vWF，vWFpp，tPA，PAI-1浓度，血糖，血脂检测，利用超声技术进行颈动脉IMT与血流速度的检测。结果：低年龄组平均IMT(0．71&;#177;0．09)min，平均血流速度(44．4&;#177;13．2)cm／s与高年龄组平均IMT(0．82&;#177;0．10)min，平均血流速度(32．8&;#177;9．2)cm／s比较，差异有显著性意义(t=2．936，P&;lt;0．01；t=3．092，P&;lt;0．05)；高脂血症者tPA浓度[(23．8&;#177;16．5)μg／L]高于血脂正常者tPA浓度[(9．4&;#177;8．0)μg／L，t=2．690，P&;lt;0．05]，高血压者PAI-1浓度[(93．3&;#177;15．8)μg／L]高于血压正常者PAI-1浓度[(82．94-5．2)μg／L，t=2．578，P&;lt;0．05]，糖尿病者vWFpp水平[(7334-220)μg／L]高于正常者vWFpp水平[(571&;#177;176)μg／L，t=2．089，P&;lt;0．05]；vWF与胆固醇，vWFpp呈正相关(r=0．374，r=0．385，P&;lt;0．05)；vWFpp与血糖呈正相关(r=0．469，P&;lt;0．05)。与tPA，PAI-1有明显的正相关性(r=0．509，r=0．527，P&;lt;0．01)。结论：vWF，vWFpp均可反映内皮细胞的损伤，vWFpp与机体纤溶系统的状态密切相关。     

慢性心力衰竭患者肾素血管紧张素系统对纤溶功能的影响

目的研究慢性心力衰竭(CHF)患者肾素血管紧张素系统(RAS)和纤溶功能的变化,及RAS对纤溶功能的影响.方法 CHF患者60例.健康体检者20例(正常对照组).用放射免疫法(RIA)测定CHF组和对照组血浆肾素活性(PRA)、血管紧张素Ⅱ(Ang Ⅱ)、醛固酮(ALD)水平,并用酶联免疫吸附法(ELISA)测定血浆组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物-1(PAI-1)抗原含量.结果 CHF组血浆PRA、AngⅡ、ALD、t-PA和PAI-1平均水平都明显高于对照组(P<0.01).CHF患者血浆PAI-1和AngⅡ水平增高程度随心力衰竭恶化而愈加明显.CHF患者血浆PAI-1抗原含量与AngⅡ水平呈正相关(r=0.994, P<0.01).结论在CHF的发展过程中RAS对纤溶功能具有重要调节作用.     

先天性纤溶酶原激活物抑制剂-1缺乏症的诊断研究

目的　诊断 1例先天性纤溶酶原激活物抑制剂 1(PAI 1)缺乏症患者并研究其基因异常。方法　用发色底物法、酶联免疫吸附实验测定组织型纤溶酶原激活物 (tPA)、α2 纤溶酶抑制剂因子(α2 PI )与PAI 1的活性和 (或 )抗原 ,PCR法与DNA测序分析患者的基因异常 ,用限制性内切酶PshAⅠ对患者和 6 0名正常人PCR产物酶切以排除基因多态性。结果　患者优球蛋白溶解时间 (ELT) 70min ,血浆中加入生理浓度的PAI 1(5 0ng ml)后ELT延长至 12 0min ,PAI 1活性 0 .0 4AU ml,PAI 1抗原 5 .6ng ml,α2 PI活性、F活性及tPA抗原和活性均正常。PCR测序证实患者PAI 1基因外显子 2第 4 3位核苷酸G→A杂合性改变 ,导致信号肽第 15位的丙氨酸突变为苏氨酸。酶切鉴定排除了多态性。结论　报道国内首例PAI 1缺乏症患者 ,其基因改变可能为复合杂合子 ,其中之一为Ala15Thr,该突变为一种国际上尚未报道的新的基因突变。     

OP 0413-0445

Objective To test the hypothesis that alveolar plasminogen activator inhibitor-1 (PAI-1) can identify patients with witnessed aspiration at risk for progression to acute respiratory distress syndrome (ARDS).Design Prospective observational study.Setting Medical intensive care unit in a tertiary care center.Patients Fifty-one patients with witnessed aspiration who had a PaO₂/FIO₂<300 for a period no less than 4 h from admission.Interventions Alveolar fluid sampling was performed within 8 h of intubation via luminal suction of the distal airways using a 13-Fr catheter. Plasma levels were collected simultaneously by venipuncture.Measurements and results Alveolar PAI-1 antigen levels were more than five times higher in those who progressed to ARDS than in those with uncomplicated aspiration pneumonitis (2687±1498 ng/ml vs. 587±535 ng/ml, respectively; p<0.001), while plasma levels of PAI-1 antigen were not significantly different between the two groups. The measured activity of PAI-1 antigen paralleled the levels observed in both media. A cut-off level of alveolar PAI-1 >1518 ng/ml was found to be 82.4% (56.6%–96.0%) sensitive and 97.1% (84.6%–99.5%) specific in predicting progression to ARDS. There was also a significant inverse relationship between elevation of PAI-1 antigen levels and the degree of lung injury as assessed by the days of unassisted ventilation (r²=0.37; p<0.001).Conclusions Elevation of alveolar PAI-1 antigen levels postaspiration is the consequence of local rather than systemic activation of the fibrinolytic system. Measurement of alveolar PAI-1 antigen levels can be a useful clinical marker in predicting progression to ARDS after gastric aspiration.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

Lipoprotein(a), tissue plasminogen activator and plasminogen activator inhibitor 1 levels in hyperlipidaemic patients in Kuwait

Plasma levels of lipoprotein(a) [Lp(a)], tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were assessed in addition to anthropometry and levels of glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apo A1 and B in 73 patients (36 men and 37 women) with primary hyperlipidaemia (group NDHL) in Kuwait. Lp(a) levels (212 mg L^?1, 8–600 mg L^?1, median and range) were similar to those obtained in a matched group of 32 non-insulin-dependent diabetes mellitus (NIDDM) patients with hyperlipidaemia (218 mg L^?1, 50–610 mg L^?1) and slightly higher, although not significantly so (P = 0.06), than levels seen in 68 healthy normolipidaemic control subjects (182 mg L^?1, 70–488 mg L^?1). tPA levels (8.4 ng mL^?1, 3.8–18.4 ng mL^?1, median and range) in group NDHL were lower than in the diabetic group (11.4 ng mL^?1, 5.2–14.2 ng mL^?1) but higher than in the healthy control subjects (7.4 ng mL^?1, 2.8–12.6 ng mL^?1). PAI-1 levels in group NDHL (40.4 ng mL^?1, 8.6–55 ng mL^?1, median and range) were higher than in the control subjects (32.5 ng mL^?1, 14.6–46.4 ng mL^?1) but lower than in diabetic patients (43.8 ng mL^?1, 15.6–55 ng mL^?1). Hyperlipidaemia phenotype (hypercholesterolaemia or hypertriglyceridaemia) did not influence tPA and PAI-1 levels, but Lp(a) levels were significantly lower with hypertriglyceridaemia. Gender, cigarette smoking and racial origin (Kuwaitis, other Arabs or South Asians) did not affect Lp(a), tPA and PAI-1 levels, but tPA levels were higher in postmenopausal subjects. Low-density lipoprotein (LDL) levels (whether in total cholesterol or as apo B) correlated significantly (P < 0.05) with Lp(a) levels. tPA levels were correlated with age and the plasma levels of glucose and uric acid (P < 0.05); this correlation with glucose may explain the high levels associated with diabetes, whereas the age association might account not only for the differences observed between group NDHL and the younger control group but also for the higher levels in the postmenopausal women. PAI-1 levels correlated with tPA and triglyceride (TG) levels in the groups of subjects (normo- and hyperlipidaemic). In the normolipidaemic control group, the significant associations of tPA and PAI-1 were with body mass, expressed as the body mass index or the waist–hip ratio. These results suggest that different factors influence the plasma levels of the prothrombotic factors Lp(a), tPA and PAI-1 in healthy control subjects and in patients with hyperlipidaemia. In the latter, hyperlipidaemia phenotype, age, glycaemic status and uric acid levels are important determinants of the levels of these prothrombotic variables, whereas in the healthy, young control population, body mass was the single important association with tPA and PAI–1.     

肾病综合征患者血浆脂蛋白(a)水平与部分纤溶指标活性的关系

目的研究肾病综合征患者血浆脂蛋白(a)与部分纤溶指标活性的关系。方法应用酶联免疫吸附试验(ELISA)分别测定60例肾病综合征患者及51名健康对照者的血浆脂蛋白(a)浓度,并以底物显色法测定其组织型纤溶酶原激活剂(tPA)及其抑制物(PAI)活性。结果肾病综合征患者血浆脂蛋白(a)浓度和PAI活性明显升高,tPA活性明显降低;脂蛋白(a)浓度与血浆尿素氮水平、PAI活性均呈正相关;脂蛋白(a)浓度与tPA活性呈负相关。结论肾功能对血浆脂蛋白(a)浓度起一定的调节作用,脂蛋白(a)水平的升高与纤溶活性低下有关。     

Regulation of local availability of active tissue-type plasminogen activator in vivo in man.

Free, biologically active tissue-type plasminogen activator (tPA) is the main initiator of intravascular fibrinolysis, but little is known about the regulation of active tPA on the organ level. The aim was to investigate if the local availability of active tPA on the organ level depends on the local release rate of tPA or the arterial input of tPA and plasminogen activator inhibitor type 1 (PAI-1). Also, we wanted to evaluate if plasma levels predict capacity for endothelial release of fibrinolytic proteins. Invasive perfused-forearm studies were performed in 96 healthy subjects. Local release rates of fibrinolytic proteins were assessed at baseline and during endothelial stimulation. Stimulation by methacholine and desmopressin induced a 6- and 12-fold increase in total tPA release rates, respectively. With increasing local release rates of tPA a gradually closer correlation emerged between the total tPA secretion and the forearm output of active tPA (from r = 0.102, ns to r = 0.85, P < 0.0001). Forearm availability of active tPA was not related to arterial input of either tPA or PAI-1. Release rates and plasma levels of tPA were not correlated. Baseline release rates of active tPA increased to noon. The major determinant for the local availability of active tPA is the capacity of the endothelium to release tPA rather than the arterial input of PAI-1 or tPA. Despite a molar excess of PAI-1, the majority of tPA released during stimulation does not undergo local inactivation. The capacity to release tPA locally cannot be predicted from its plasma concentration.     

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。     

阻塞性睡眠呼吸暂停低通气综合征患者血管内皮细胞及纤溶系统功能变化

目的：探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血管内皮细胞及纤溶系统功能变化。方法：根据多导睡眠呼吸监测仪监测结果，选择年龄、性别、体重指数(BMI)无明显差异的OSAHS患者52例和健康者48例。以Clauss法测定纤维蛋白原(Fg)，以发色底物法测定组织纤溶酶原激活物活性(tPA：A)、纤溶酶原激活物抑制物-1活性(PAI-1：A)，以酶联免疫法测von Willebrand因子含量(vWF)、组织纤溶酶原激活物含量(tPA：Ag)、纤溶酶原含量(PLg：Ag)和纤溶酶原激活物抑制物-1含量(PAI-1：Ag)。结果：与对照组比较，(3SAHS组vWF、Fg、PAI-1：A、PAI-1：Ag水平明显升高，PLg：Ag、tPA：Ag含量明显降低，tPA：A无明显变化。结论：OSAHS患者血管内皮细胞功能受损，纤溶系统功能降低。     

Effect of Low Dose Aspirin on Augmented Piasminogen Activator Inhibitor Type 1 Activity in Patients with Permanent Pacemakers

To clarify the activity states of coagulation and fibrinolysis in patients with a permanent pacemaker, we studied 29 patients more than 4 months after operation. They were divided into a single pacemaker lead group (S, n = 14) and a double lead group (D, n = 15). Prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, tissue-type plasminogen activator (tPA) activity, plasminogen activator inhibitor type-1 (PAI-1) activity, and platelet aggregation were measured and compared to those in an age-matched control group (C, n - 7). The effects of low dose aspirin (81 mg/day) in the patients (n = 21) were also studied 2 weeks after administration. PAI-1 activity in groups S and D was significantly higher than that in the group C (53.5 ± 36.5, 86.8 ± 59.2 ng/ mL vs 19.4 ± 7.2 ng/mL; P < 0.01 and P < 0.005). Platelet aggregation induced by collagen was slightly higher in groups S and D than group C. Other parameters were not significantly different. In the patients, low dose aspirin significantly suppressed collagen induced platelet aggregation (71.8 ± 20.3% vs 41.7 ± 28.3%; P < 0.005), but not PAI-1 activity. tPA activity was increased significantly by the low dose aspirin administration (3.94 ± 1.85 ng/mL vs 2.48 ± 1.19 ng/mL; P < 0.005). Thus, PAI-1 activity in patients with a permanent pacemaker is elevated, and the activity is not suppressed by low dose aspirin unlike the platelet aggregation.