丹参酮对老年冠心病患者血清tPA、PAI水平的影响

目的观察丹参酮治疗老年冠心病的机制。方法将78例老年冠心病患者随机分为两组,对照组采用常规治疗,治疗组在此基础上加用丹参酮50mg静滴,1次／d,用药均2周。采用发色底物法和ELISA法测定两组血浆组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制因子-1（PAI-1）活性及含量。结果与治疗前和对照组比较,治疗组血浆PM-1活性及水平下降（P〈0．05）,t-PA活性及水平升高（P〈0．05）。结论丹参酮治疗老年冠心病效果确切,其机制可能为调控内源性纤溶活性及血管内皮功能。     

复方丹参滴丸对冠心病患者纤溶系统t-PA、PAI-1含量与活性的调控

目的观察复方丹参滴丸对冠心病患者内源性纤溶活性及血管内皮功能的影响，探讨其作用机制。方法冠心病患者78例，随机分为对照组和复方丹参滴丸组。对照组采用常规治疗；复方丹参滴丸组在常规治疗基础上加用复方丹参滴丸每次10粒，每日3次。两组用药时间均为4周。比较治疗前后血浆组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制因子-1（PAI-1）活性及浓度。结果复方丹参滴丸治疗4周后，患者血浆PAI-1活性及浓度下降（P〈0．05），t—PA活性及浓度含量升高（P〈0．05），与治疗前比较差异有统计学意义；常规治疗组治疗前后t-PA和PAI-1活性差异无统计学意义。结论复方丹参滴丸可有效地调控改善冠心病患者内源性纤溶活性及血管内皮功能。     

2型糖尿病纤溶系统变化与胰岛素抵抗的关系

目的探讨2型糖尿病患者纤溶活性变化与胰岛素抵抗之间的关系。方法采用酶联免疫吸附法测定63例2型糖尿病患者（包括无血管并发症组30例和有血管并发症组33例）和25例正常对照者血浆组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）含量,结合临床资料分析其变化趋势及影响因素。结果2型糖尿病患者血浆t-PA含量明显降低（P〈0．01）,而PAI-1含量明显升高（P〈0．01）,合并血管病变者,此变化更为显著（均P〈0．001）。多元逐步回归分析显示,HOMA模型胰岛素抵抗指数（HOMA—IR）是PAI-1升高的独立危险因素。结论2型糖尿病患者纤溶活性降低,胰岛素抵抗在降低其纤溶活性,并发血管病变中起了重要作用。     

吡格列酮对2型糖尿病患者动脉粥样硬化相关因素的影响

目的探讨吡格列酮预防2型糖尿病动脉粥样硬化的可行性及机制。血清超敏C-反应蛋白（hs-CRP）、纤溶酶原激活物抑制剂-1（PAI-1）、P-选择素及胰岛素抵抗等动脉粥样硬化相关因素的影响。方法对30例2型糖尿病患者加用吡格列酮15mg／d,共12周。治疗前后测定血清超敏C-反应蛋白（hs—CRP）、纤溶酶原激活物抑制剂-1（PAI-1）、P-选择素及胰岛索抵抗指数、血脂等动脉粥样硬化相关指标。结果治疗后hs—CRP、PAI-1及P．选择素、胰岛素抵抗指数均显著下降（P〈0．05）,血脂各项指标均无显著变化。结论吡格列酮有助于预防2型糖尿病动脉粥样硬化;其机制为降低2型糖尿病患者血清hs—CRP、PAI-1及P-选择素水平及胰岛素抵抗程度。     

葛根素对冠心病患者胰岛素抵抗及内皮纤溶功能的影响

将72例冠心病（CHD）患者随机分为常规组（33例）和葛根素组（39例），均于治疗前及治疗结束时检测其血糖，胰岛素，纤溶指标，计算胰2岛素敏感性指数（ISI），并行静脉闭塞试验（VOT）；同时选择30例健康人作为对照组。结果显示：（1）与对照组比较，CHD患者的血浆胰岛素（FINS）浓度增高（P＜0．05），ISI降低（P＜0．05），VOT前及VOT时内皮细胞型纤溶酶原激活物（t-PA)活性降低（P＜0．01），纤溶酶原激活物抑制物－1（PAI－1）活性增高（P＜0．01）。FINS，ISI与纤溶指标存在高度线性相关意义。（2）葛根素组治疗后FINS，PAI－1下降（P＜0．01），ISI，VOT前及VOT时t-PA增高（P＜0．05，＜0．01），与常规组治疗后比较均具有显著性差异（P＜0．05，P＜0．01）。认为葛根素能改善CHD患者的胰岛素抵抗（IR）及与其密切相关的内皮纤溶功能。     

不同剂量重组组织型纤溶酶原激活剂溶栓治疗急性心肌梗死的疗效评价

目的比较50rag和100mg重组组织型纤溶酶原激活剂（rt—PA）溶栓治疗急性心肌梗死疗效的差别。方法入选78例急性心肌梗死患者,其中50mg组35例,100mg组43例。两组患者都常规应用阿司匹林和肝素等药物,分别静脉注射重组组织型纤溶酶原激活剂（rt—PA）50mg和100mg。比较两组患者溶栓后的冠状动脉开通率（根据临床判定）,发病30d左室射血分数和死亡率。结果冠状动脉开通率50mg组为77．1％（27例）,100mg组为81．4％（35例）;30d左室射血分数分别为（48．7±7．2）％,（50．0±7．6）％;30d病死率分别为5．7％（2例）,4．7％（2例）,两组间比较均无统计学意义。结论100mg和50mg重组组织型纤溶酶原激活剂（rt—PA）对于国人急性心肌梗死的溶栓疗效相似。     

格列美脲与格列本脲治疗2型糖尿病疗效的系统评价

目的系统评价格列美脲与格列本脲治疗T2DM的疗效。方法计算机检索PubMed、万方等数据库从建库至2010年12月间的有关文献。按Cochrane系统评价的方法评价纳入研究的质量,使用Review Manager4．2软件进行荟萃分析。结果共纳入9个随机对照试验。结果显示：格列美脲在降低HbA1c[P=0．08,加权均数差（WMD）=-0．18,95％CI（-0．39,0．02）]、FPG[P=0．06,WM=-0．46,95％CI（-0．94,0．01）]、餐后血糖[P=O．73,WMD=-0．16,95％CI（-1．08,0．76）]、TC[P=0．22,WMD=-0．2,95％CI（-0．51,0．12）]和TG[P=0．06,WMD=-0．30,95％CI（-0．61,0．01）]方面与格列本脲无差异;在相同血糖水平下,格列美脲组FIns[P〈0．05,WMD=-0．83,95％CI（-1．21,0．45）]及餐后胰岛素[P〈0．05,WMD=-5．94,95％CI（-8．79,-3．10）]升高程度低于格列本脲组;低血糖发生率格列美脲组低于格列本脲组[P〈0．05,RR=0．66,95％CI（0．53,0．81）];在降低BMI方面格列美脲优于格列本脲[P=0．02,WMD=-1．49,95％CI（-2．7,-0．27）]。结论与格列本脲相比,格列美脲在降低血糖的同时,还能改善胰岛素抵抗及减轻体重,且低血糖发生率低,是安全有效的治疗T2DM的药物。     

重组葡激酶与重组组织型纤溶酶原激活剂治疗急性心肌梗死的随机多中心临床试验

目的研究新型溶栓剂——重组葡激酶（r-Sak）治疗急性心肌梗死（AMI）的冠状动脉通畅率、临床疗效及安全性。方法本研究为多中心、随机、平行对照临床试验,入选发病12h内、年龄≤70岁、ST段抬高的AMI患者,随机分为r-Sak组104例,给予r-Sak 3mg静注,12mg于30min内静脉输注,总量15mg;重组组织型纤溶酶原激活剂（rt-PA）组106例,8mg静注,42mg在90min内输注,总量50mg。全部患者给予阿司匹林和静脉输注肝素,于用药90min行冠状动脉造影,对TIMI血流0～2级者行补救性PCI。结果主要终点：用药90min冠状动脉通畅率（TIMI血流2级或3级）,r-Sak组明显高于rt-PA组（77.8％比63.6％,P=0．0277）,TIMI 3级者两组间差异无统计学意义（57．6％比48．5％,P=0．1929）;1个月内死亡（8,7％比5,7％,P=0．3997）、非致死性再梗死（2,9％比3．8％,P=1．0000）、心肌缺血复发（8,7％比16．0％,P=0.1043）和复合临床终点（18．3％比21．7％,P=0。5345）两组间差异均无统计学意义。次要终点：r-Sak组出血发生率（28．8％）与rt-PA组（27．4％）比较,差异无统计学意义（P=0,8105）,其中严重或威胁生命的出血,两组间差异亦无统计学意义（1．9％比3．8％）,r-Sak组脑出血1例（0．96％）,rt-PA组脑出血4例（3．85％）。无其他药物相关的严重不良反应及过敏反应发生。结论r-Sak是一种安全、有效的治疗AMI的溶栓药物,其疗效及安全性至少与rt-PA 50mg相似。     

同型半胱氨酸对人脐静脉内皮细胞纤溶系统的影响

目的探讨同型半胱氨酸（homocysteine,Hcy）对血管内皮细胞纤溶系统影响。方法（1）将体外培养的人脐静脉血管内皮细胞（HUVEC）分为10个实验组（0、10、50、200、500μmol／L Hcy组及叶酸和上述各Hcy点共同培养组）,培养24h后,酶联免疫吸附实验法（ELISA）测定各组细胞上清液中纤溶酶原激活剂（plasminogen activator,tPA）及纤溶酶原激活物抑制剂1（plasminogen activator inhibitor1,PAI-1）抗原含量,逆转录聚合酶链反应分析（RT-PCR）法分析各组tPA及PAI-1的mRNA表达水平。（2）急性心肌梗死（AMI）患者53例及健康对照组48例,ELISA测定空腹血浆tPA及PAI-1含量,高效液相色谱法测定血浆Hcy水平。结果（1）500μmoL／L Hcy组PAI-1抗原及mRNA表达水平均明显增高（P〈0．05）。（2）以单纯培养基为对照组,生理浓度Hcy组内皮细胞tPA抗原合成及mRNA表达明显增高（P〈0．05）,而以10μmoL／L Hcy组为对照组时,500μmoL／L Hcy组tPA抗原合成及mRNA表达水平则明显减少（P〈0．05）。（3）500μmoL／L Hcy与叶酸共同培养组和单纯Hcy组相比,可以明显提高内皮细胞tPA抗原的合成及mRNA表达,减少PAI-1抗原合成及mRNA表达（P〈0、05）。（4）AMI组Hcy、tPA及PAI-1均明显高于健康对照组（P〈0．05）。结论在体外细胞时,超生理浓度Hcy可以通过下调tPA、上调PAI-1的mRNA表达,减少内皮细胞tPA抗原的分泌及增加PAI-1抗原的合成,可能降低纤溶系统的活性。叶酸则可以减少Hcy引起内皮细胞纤溶系统的损害,起到保护作用。Hcy是AMI的一个独立危险因素。     

老年高血压病患者性激素与血管内皮功能的关系

为研究老年高血压病患者性激素,vWF含量和纤溶活性的改变及其相关性,分别采用放射免疫法,酶联免疫吸附法和发色底物法测定了66例（女34例,男32例）I,II期老年高血压病患者和32例（女16例,男16例）老年正常人的雌二醇,睾酮及内皮损伤特异性标志物－von Willebrand因子含量,以及组织型纤溶酶原激活物和纤溶酶原激活物抑制物活性,并进行了相关性分析,结果发现,老年女性高血压病雌二醇水平,组织型纤溶酶原激活物活性明显低于老年女性正常对照组（P＜0．01,P＜0．05）,而von Willebrand因子含量,纤溶酶原激活物抑制物活性明显高于正常对照组（P＜0．05,P＜0．01）,老年男性高血压病组睾酮水平,组织型纤溶酶原激活物活性明显低于老年男性正常对照组（P＜0．05,P＜0．01）,von Willebrand因子含量,纤溶酶原激活物抑制物活性显著高于正常对照组（P＜0．05,P＜0．01）,老年女性高血压病组雌二醇水平与von Willebrand因子含量呈显著负相, 结果提示,老年女性高血压病患者雌二醇水平明显降低,而男性睾酮水平下降,两者都存在明显的内皮损伤,纤溶活性异常,雌二醇可能通过对血管内皮功能的有利影响而对女性高血压起保护作用。     

培哚普利对慢性心力衰竭患者血浆t-PA和PAI-1水平的影响

目的评价培哚普利对慢性心力衰竭(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)水平的影响。方法采用酶联免疫吸附法测定60例CHF患者(CHF组)及20例健康人(正常对照组)血浆t-PA、PAI-1水平。CHF组患者又随机均分为常规治疗亚组和培哚普利亚组。培哚普利亚组在常规治疗基础上加用培哚普利2~4mg,每日1次。所有CHF患者治疗2周后复测血浆t-PA、PAI-1水平。结果CHF患者血浆t-PA、PAI-1水平比正常对照组明显增高(P<0.01)。治疗后,培哚普利亚组血浆PAI-1水平比常规治疗亚组明显降低(P<0.01),血浆t-PA水平比常规治疗亚组明显升高(P<0.01)。结论培哚普利不仅可降低PAI-1水平,而且可升高t-PA水平,改善内源性纤溶功能。     

Hypofibrinolysis in patients with hypercoagulability: The roles of urokinase and of plasminogen activator inhibitor

The prevalence of abnormalities of fibrinolysis in patients with venous thromboembolism is as yet unknown. Defined abnormalities include congenital dysfunction and deficiency of plasminogen, and probably impaired plasminogen activation secondary to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) or to impaired release of tissue plasminogen activator (tPA). In this preliminary study, we analyzed plasma samples from 21 patients for whom an investigation for possible thrombophilia was requested. Twenty of the patients had venous thromboembolism, and one had arterial thrombosis at an early age. Two patients had deficiency of protein C or protein S, but no other recognized biochemical disturbances related to thrombophilia were identified. Patient samples and plasma from 25 normal controls were assayed for tPA activity, PAI-1 activity, and urokinase (uPA) activity and antigen. tPA activity and antigen were not significantly different in patients than in controls. PAI-1 activity was significantly greater in patients (P < 0.0001). uPA activity was not different in the two groups. However, uPA antigen was significantly reduced in patients compared to controls (P = 0.001). These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI-1 activity but also by reduced total uPA concentration. © 1993 Wiley-Liss, Inc.     

A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction

The balance between the coagulation system generating fibrin and its subsequent removal by the fibrinolytic system determines the fate of fibrin deposited in the vascular system. In a prospective study, selected haemostatic variables assessing this balance were determined in plasma samples from 20 consecutive patients admitted with unstable angina pectoris. Over a follow-up period of 6 years, eight patients developed myocardial infarction, whereas 12 patients did not. There was no significant difference between the two groups in the median plasma concentrations of thrombin-antithrombin III complexes reflecting the coagulant activity. The infarction group was characterized by a significantly lower median activity of tissue plasminogen activator in plasma euglobulins (P less than 0.05), a higher median concentration of tissue plasminogen activator antigen in plasma (P less than 0.05) and a tendency to higher plasma levels of antigenic and functional plasminogen activator inhibition. In all patients, the activities of tissue plasminogen activator inhibitor and of tissue plasminogen activator were significantly associated (rs = -0.4811, P less than 0.05). We conclude that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.     

On the Usefulness of Fibrinolysis Variables in the Characterization of a Risk Group for Myocardial Reinfarction

ABSTRACT. In a prospective study selected fibrinolysis variables were assessed in plasma samples from 29 consecutive patients recovering a first instance of acute myocardial infarction and the results were correlated with reinfarction during the next four years. Nine patients suffered a reinfarction leaving a group of 20 patients without evidence of relapse. The reinfarction group was characterized by lower tissue plasminogen activator activities in plasma euglobu-lins (p<0.05), significantly higher plasma concentrations of tissue plasminogen activator antigen (p<0.002) and a tendency to a higher plasma level of plasminogen activator inhibition capacity. There were no significant differences between the groups in plasma concentrations of plasminogen, histidine-rich glycoprotein, plasminogen kringle-4-binding-protein, and α₂-antiplasmin.     

Tissue plasminogen activator levels in different types of polycythemia

The plasma level of tissue plasminogen activator antigen (t-PA-Ag) was examined in 86 patients with polycythemia (29 polycythemia vera, 11 secondary polycythemia and 46 with spurious polycythemia) and 24 healthy volunteers. Tissue plasminogen activator antigen was significantly decreased in patients with polycythemia vera in comparison with healthy controls. On the other hand, in patients with spurious polycythemia and secondary polycythemia t-PA-Ag concentration was significantly increased. There was no significant difference in t-PA-Ag levels in polycythemic patients with or without thromboembolic disease. A significant correlation was detected between t-PA-Ag level and hemoglobin or hematocrit concentration in patients with polycythemia vera (p = 0.02, r = 0.43). However, in patients with secondary polycythemia and spurious polycythemia, no significant correlation between t-PA-Ag and hemoglobin level was found. Plasminogen activator inhibitor (PAI) levels in patients with polycythemia vera and healthy volunteers did not differ significantly.     

磁化支架安置术后血浆纤溶活性变化及临床意义

目的 :观察冠心病患者冠状动脉内支架安置术 （ICS）后冠状窦血浆组织型纤溶酶原激活物 （t- PA）和纤溶酶原激活物抑制剂 - 1（PAI- 1）活性的动态变化 ,探讨磁化支架对术后再狭窄防治的作用机制。方法 :冠心病患者 38例 ,随机安置普通支架 18例 （I组 ） ,磁化支架 2 0例 （II组 ） ,分别于 PTCA前、ICS后即刻、6 h时自冠状窦采血来检测血浆 t- PA和 PAI- 1的活性。结果 :两组患者的 t- PA活性在术后即刻均降低 ,而术后 6 h II组的 t- PA活性较之 I组有明显恢复 （P<0 .0 5 ）。相反 ,术后即刻两组患者的 PAI- 1活性均明显升高 （P<0 .0 1） ;然而 ,在术后 6 h,II组的 PAI- 1活性已恢复到术前水平 （P<0 .0 5 ）。结论 :磁化支架可有效促进冠脉循环纤溶活性的恢复 ,可能对再狭窄有防治作用。     

Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma

BACKGROUND AND METHODS: The plasminogen activation system plays a crucial role in the process of cancer invasion and metastasis. To evaluate the most effective factor in the invasion, metastasis and prognosis of hepatocellular carcinoma (HCC), we examined urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1, PAI-2 and uPA activity by enzyme-linked immunosorbent assays (ELISA) in HCC tissues obtained from 46 patients. The results were compared with the patients' clinicopathological features and prognoses. RESULTS: Of the clinicopathological features, only histological portal involvement or intrahepatic metastasis, or both (INV), was significantly correlated to the disease-free survival rates (DFS; P < 0.05). The levels of uPA, PAI-1 and PAI-2 antigens were significantly associated with INV and histological grade. The DFS was not different, however, between cases with uPA, PAI-1 and PAI-2 values above and below the median. The high levels of uPA activity were closely related to INV (P < 0.001), and the activity gradually raised histological grades (P < 0.0001). The DFS was significantly different between patients with uPA activity below and above the median (0.70 ng/mL; P = 0.0092); it was also significantly different between such patients without INV (P < 0.05). CONCLUSIONS: Urokinase-type plasminogen activator activity may be the most sensitive factor affecting HCC invasion in the plasminogen activation system and a strong predictor for the recurrence of HCC. We suggest that cases with uPA activity of more than 0.70 ng/mL should be carefully followed up for possible HCC recurrence.     

t-PA、PAI活性测定在早期糖尿病肾病临床中的意义

目的 探讨2型糖尿病（T2DM）患者及糖尿病肾病（DN）患者中尿白蛋白排泄率（UAER）与血浆组织型纤溶酶原激活物（t-PA）、纤溶酶原激活物抑制物（PAI）活性的相关性。方法 选择60例T2DM病人，根据UAER分为单纯糖尿病（DMa）组、微量白蛋白尿组（DMb）和临床蛋白尿组（DMc）。此外，还选择了30例健康人作为对照组。采用发色底物显色法测定血浆t-PA和PAI的活性，并对其相关性进行统计分析。结果 （1）对照组、DMa组、DMb组和DMc组血浆卜PA活性递减，PAI的活性递增，各组比较有显著性差异（P〈0．01）。（2）t-PA与UAER呈负相关（r=0．615，P=0．000），PAI和UAER呈正相关（r=0．721，P=0．000）。结论 DN早期即有纤溶活性低下；t-PA和PAI可能作为DN肾脏损害程度的佐证，对指导临床用药以缓解或延迟DN的发生具有重要意义。     

Plasma levels of endothelial-derived haemostatic factors in autoimmune thrombocytopenia and haemolytic anaemia

The endothelial cell-synthesized haemostatic factors tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and von Willebrand factor (vWF) were assayed in a cross-sectional study of patients with immune thrombocytopenia (ITP) (n = 12) and autoimmune haemolytic anaemia (AIHA) (n = 3), and compared with a simultaneously selected contrast group of other hospitalized patients with obscure blood cytopenia at the time of sampling. All three factors were grossly elevated in both the study group and the contrast group. In the autoimmune patient group, the three haemostatic variables were significantly correlated with orosomucoid levels, demonstrating the acute-phase nature of the increased levels of vWF, tPA and PAI. These findings support the view that haemostatic factors of the vessel wall are implicated in the pathophysiology of a wide spectrum of diseases.