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。     

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.     

高原肺水肿血浆纤溶系统的变化

目的　观察高原肺水肿 (HAPE)患者血浆纤溶系统的变化 ,探讨其发病学意义。方法　测定 37例HAPE患者治疗前后血浆组织型纤溶酶原激活物 (tPA)及纤溶酶原激活物抑制物 (PAI- 1)的含量 ,并以 2 0名健康志愿者作对照。结果　HAPE患者治疗前血浆tPA含量为 (0 39± 0 19)× 10 3 IU/L ,显著低于正常对照组的 (0 5 9± 0 17)× 10 3 IU/L(P <0 0 1) ,治疗后tPA为 (0 4 9± 0 16 )× 10 3 IU/L ,较治疗前显著升高 (P <0 0 5 ) ;治疗前PAI- 1含量为 (6 6 4± 1 6 3)× 10 3 AU/L ,显著高于正常对照组的 (4 87± 1 34)× 10 3 AU/L(P <0 0 1) ,治疗后PAI- 1含量为 (5 81± 1 5 4 )× 10 3 AU/L ,较治疗前显著降低 (P <0 0 5 )。结论　HAPE患者纤溶系统呈失衡性改变 ,可能作为急性肺动脉高压成因之一而参与HAPE的发病过程。     

急性脑梗死患者血浆组织型纤溶酶原激活物与抑制物活性的动态变化

目的观察急性脑梗死不同时期患者血浆纤溶活性的动态变化,探讨其变化在病情发展中的作用。方法采用发色底物显色法测定60例脑梗死患者急性期与恢复期和60例同期住院非心、脑血管疾病患者血浆组织型纤溶酶原激活物(tissue-plasminogenactivator,t-PA)、纤溶酶原激活抑制物(plasminogenactivatorinhibitor,PAI)活性。结果脑梗死急性期组与恢复期组和对照组相比,t-PA活性明显减低,PAI活性显著增高(P均<0.01)。恢复期组与对照组比较差异无显著性意义(P>0.05)。结论急性脑梗死患者纤溶平衡失调,故检测其血浆t-PA,PAI活性动态变化可作为脑梗死诊断与治疗的一个客观参考指标。     

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。     

下肢深静脉血栓形成患者凝血、抗凝和纤溶功能的检测

目的 :通过检测下肢深静脉血栓形成 (LDVT)患者凝血、抗凝和纤溶系统各项指标 ,探讨高凝状态在LDVT发病机制中的重要作用 ,指导临床采用合理的预防及治疗措施。方法 :以 74例健康查体者作为对照组 ,测定 74例LDVT患者的血小板数量 (BPC)、血小板聚集率 (PAgT)、血小板表面α颗粒膜蛋白 (GMP - 14 0 )分子数 ;血浆凝血酶原时间 (PT)、凝血酶时间 (TT)、部分凝血活酶时间 (APTT)、纤维蛋白原 (Fg)及血管性血友病因子 (VWF)含量 ;抗凝血酶III活性 (AT -IIIA)、蛋白C活性 (PC)、总蛋白S含量 (PS) ;纤溶酶原 (PIg)活性、组织型纤溶酶原激活物活性 (tPA -A)及纤溶酶原激活物抑制物— 1(PAI- 1)的含量。结果 :与正常对照组相比 ,LDVT患者的PAgT、GMP - 14 0分子数明显升高 (P <0 .0 5 ) ;PT、TT、APTT、AT -IIIA、PC、PS、PIg活性、tPA -A水平均明显降低 ;而Fg、VWF及PAI- 1含量均明显增高 ,与正常对照组有极显著差异 (均P <0 .0 0 1)。结论 :血液凝血、抗凝和纤溶活性异常所致的高凝状态在LDVT发病机制中占有重要地位 ,临床应采用凝血、抗凝和纤溶指标联合指导LD VT的防治 ,以取得最佳疗效     

纤溶酶原激活物及其抑制剂-1的血浆含量测定在急性肺血栓栓塞症中的意义

目的探讨在急性肺血栓栓塞症(APE)发病中的组织型纤溶酶原激活物(tPA)及其抑制剂-1(PAI-1)的血浆含量、作用及其该病诊断中的意义。方法,对44例APE患者和56例健康正常对照者应用酶联免疫吸附双抗体夹心法(ELISA法)定量测定血浆tPA和PAI-1抗原水平。结果与正常对照组(tPA含量为11．05ng／ml和PAI-1含量为61．31ng／m1)相比,APE组的IPA含量(33．88ng／ml)和PAI-1含量(111．50ng／ml)较高,两组间差异有显著性。在急性肺血栓栓塞症的疾病诊断中,tPA和PAI-1的血浆含量合理诊断截断点分别为21．7ng／ml和79．4ng／ml.结论急性肺血栓栓塞症的发病是由于PAI-1抗原产生和释放增多,而非tPA抗原释放或产生不足所致．tPA和PAI-1抗原血浆含量测定在APE的疾病诊断中具有要意义。     

脑梗死患者止凝血系统功能改变的研究

目的探讨脑梗死患者治疗前后D-二聚体（D-Dimer）、抗凝血酶活性（AT1A）、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）及血管性血友病因子（vWF）的变化趋势,评估上述指标在脑梗死治疗监测中的临床价值。方法采用SYSMEXCA7000型血液凝固仪测定血浆D-Dimer、tPA、PAI-1和AT1A;采用ELISA法测定vWF。结果与健康对照组比较,脑梗死患者组治疗前D-Dimer、PAI-1、vWF显著增高（P〈0．01）,t-PA显著降低（P〈0．01）,AT：A无显著性改变（P〉0．05）。脑梗死患者治疗后血浆D-Dimer、PAI-1、vWF较治疗前显著降低（P〈0．01）,tPA显著增高（P〈0．01）,AT：A在治疗前后无明显改变（P〉0．05）;GCS〉8分组和GCS≤8分组血浆胁Dimer、PAI-1、vWF明显下降（P〈0．01）,t-PA显著增高（P〈0．01）,而AT：A无明显差异（P〉0．05）。结论纤溶系统指标和vWF在脑梗死患者治疗前后发生显著改变且与病程发展相关。     

脑梗死患者检测纤溶系统及血小板参数的意义

目的探讨纤溶酶原激活剂抑制物-1、组织型纤溶酶原激活物及血小板参数在脑梗死患者中的变化。方法对60例脑梗死患者及60例健康体检者进行血小板及其参数、纤溶酶原激活剂抑制物-1、组织型纤溶酶原激活物的测量。结果与对照组相比,脑梗死患者中血小板、组织型纤溶酶原激活物含量显著低于对照组（P〈0.05）,平均血小板容积及血小板体积分布宽度及纤溶酶原激活剂抑制物-1含量显著高于对照组（P〈0.05）。结论血小板参数及纤溶酶原激活剂抑制物-1、组织型纤溶酶原激活物在脑梗死患者中有显著性改变,提示脑梗死患者存在着血小板活化及纤溶活性减低的现象,凝血系统活性改变在脑梗死患者的病情发展中起着一定的作用。     

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。     

气腹及腹腔镜手术对腹膜影响的临床研究

目的探讨腹腔镜与开腹手术中腹膜纤维蛋白溶酶的变化。方法在腹腔镜与开腹手术前、手术后立即、分别测量腹膜组织中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)浓度及t-PA活性。结果腹膜组织中t-PA浓度在腹腔镜手术和传统腹部手术2组术中均下降,但在传统腹部手术组下降更显著(P<0.05)。而腹膜组织中PAI-1水平在腹腔镜手术组术前较高(P<0.05),PAI-1浓度在传统腹部手术组术中明显升高,但在手术后,2组PAI-1浓度无显著差异。t-PA活性在2组术前、术后均无明显差异,但术中2组均显著下降(P<0.05)。结论本次临床研究结果表明:腹腔镜手术和传统腹部手术对腹膜的影响是相似的,腹腔镜手术中最初的腹膜组织中PAI-1浓度的升高由CO2气腹造成并影响腹膜组织的修复。     

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。     

Increased plasminogen activator inhibitor-1 activity in offspring of type 2 diabetic patients: lack of association with plasma insulin levels

OBJECTIVE: To determine whether a dysregulation of the fibrinolytic system exists in normal glucose tolerant offspring of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In this cross-sectional study, 32 offspring of type 2 diabetic patients and 26 subjects with no family history of diabetes were studied. With respect to the metabolic parameters, plasma fasting and 2-h postload (75 g glucose) glucose and insulin levels, total cholesterol, triglycerides, and HDL cholesterol concentrations were determined. To evaluate the status of hemostatic factors, fibrinogen, tissue plasminogen activator (tPA) antigen level, plasminogen activator inhibitor-1 (PAI-1) antigen level, and PAI-1 activity were assessed. The statistical analyses included the Mann-Whitney U test to check the significance of differences between variables in the two groups and Spearman's rank correlation tests to check the interrelationships between the hemostatic and metabolic parameters in the offspring group. RESULTS: All subjects had normal glucose tolerance according to the American Diabetes Association criteria. Plasma fasting and postload insulin concentrations were significantly higher in offspring compared with control group (P<0.00001 and P<0.01, respectively). Plasma fasting and postload glucose, fibrinogen, tPA antigen, total cholesterol, and BMI were comparable between the groups. The offspring had significantly higher waist-to-hip ratio (WHR) (P = 0.03), higher triglycerides (P = 0.01), and lower HDL cholesterol (P<0.01) compared with the control group. PAI-1 antigen level and PAI-1 activity were higher in the offspring (P = 0.05 and P = 0.04, respectively). In the offspring group, PAI-1 activity was correlated with plasma PAI-1 antigen level (r = 0.40, P = 0.02), fibrinogen (r = 0.45, P = 0.01), and HDL cholesterol (r = -0.36, P = 0.04). However, tPA antigen level, fasting and postload plasma glucose and insulin, total cholesterol, triglycerides, WHR, and BMI did not correlate with PAI-1 activity. CONCLUSIONS: These data suggest that normal glucose tolerant offspring of type 2 diabetic subjects have elevated PAI-1 activity indicating to hypofibrinolysis in this group. The elevated PAI-1 activity has no association with plasma insulin concentration.     

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.     

Vampire bats yield potent clot buster for ischemic stroke

While tissue-type plasminogen activator (tPA) is currently the standard "clot-busting" drug used to treat patients with acute ischemic stroke, another new option for treatment is now under clinical study. Desmodus rotundus plasminogen activator (DSPA), an enzyme found in the saliva of vampire bats, may offer another therapeutic option instead of tPA, a current therapy for stroke. Animal research indicates that tPA may mediate neuronal death as well as increase systemic plasminogen consumption and fibrinogenolysis. Conversely, DSPA's activity is dependent on the presence of fibrin and therefore has not been associated with the systemic plasminogen consumption and fibrinogenolysis that potentially may occur in those receiving tPA. In animal studies, tPA was found to exhibit "inherent neurotoxic properties" not seen with DSPA. In addition, DSPA may be administered up to 9 hours after the onset of symptoms, unlike tPA, which cannot be given after 3 hours without potential risk of additional brain injury. Phase II clinical trials have demonstrated a positive result in human subjects. Phase III trials are currently under way in stroke populations.     

心肌梗死患者介入术前后血小板活化及纤溶功能的变化

目的 观察急性心肌梗死（AMI）患者冠状动脉介入术后外周循环血中血小板活化及凝血-纤溶功能的变化。方法 采用ELISA检测PTCA和冠状动脉内支架术前后血小板表面α-颗粒膜蛋白（GMP-140），血管性假血友病因子（vWF)，组织纤溶酶原激活剂（t-PA)，纤溶酶原激活剂抑制物-1（PAI-1），D-二聚体（D-D）的含量。结果 35例急性心肌梗死患者PTCA术后10分钟，GMP-140，tPA和vWF明显增高，术后24小时vWF仍显著增高，结论 AMI患者介入术后血小板活化和纤溶功能均出现改变。     

Plasminogen and plasmin activity in patients with coronary artery disease

OBJECTIVE: While coronary artery disease (CAD) is associated with disturbances of the plasma fibrinolytic system, the nature of these disturbances is not fully defined. Fibrinolysis is regulated by plasmin, whose production is mediated by plasminogen activator conversion of plasminogen (Plg) to plasmin. The cascade is modulated by feedback loops that include Plg activator inhibitor 1 (PAI-1). Molecular interactions with Plg kringle domains play an important role in regulating plasmin production and its modulation of fibrinolysis. We hypothesized that interactions of tissue plasminogen activator (tPA) with Plg kringle domains regulates plasmin levels in patients with stable CAD. METHODS: Plasma was collected from patients (n = 33) with an angiographically significant CAD and controls (n = 18) with angiographically established normal or minimally diseased arteries. Plasmin activity, tPA activity, and plasma levels of Plg, PAI-1, uPA, and tPA were determined. RESULTS: CAD patients had 1.7-fold greater plasmin activity (P = 0.02) that correlated with 1.5-fold higher tPA activity when compared to controls. Epitope mapping of Plg domains showed Plg differences in epitope exposure between the two groups. Plasma from CAD patients had 50% less (P < 0.001) detectable kringle 4 and 48% less (P = 0.007) detectable kringles 1-3. CONCLUSIONS: Based on detectable differences in Plg, we conclude that in patients with stable CAD, Plg complexed with tPA exists in a conformation that enables increased tPA activity and Plg conversion to plasmin.