组织型纤溶酶原激活物在兔实验性肺血栓栓塞肺动脉中表达的动态变化及临床意义

目的通过研究兔实验性肺血栓栓塞（PTE）后组织型纤溶酶原激活物（t-PA）在肺动脉中表达的动态变化，了解急性肺栓塞后机体局部纤溶能力的变化。方法将48只日本健康大耳白兔随机分为栓塞组和对照组，栓塞组利用自体血栓经股静脉输入建立PTE模型，对照输入生理盐水。用免疫组织化学及Western blot方法检测对照组及栓塞后即刻，4、8和24h栓塞部位肺动脉组织中t-PA蛋白表达水平。结果t-PA在栓塞后8h和24h表达明显增强，而在栓塞后即刻和4h未见明显表达；半定量蛋白表达结果显示t-PA在栓塞后4h表达开始增高，栓塞后8h表达进一步增强，24h达到高峰，与各对照组比较，统计学有意义（P〈0．05），与栓塞后即刻相比有显著性（P〈0．05）。结论兔急性肺栓塞后，t—PA表达水平随时间而逐渐增高，表明了在肺动脉栓塞早期，机体的纤溶功能明显增强，这种内源性的纤溶能力的增强有利于血栓的溶解。     

组织型纤溶酶原激活物在急性肺血栓栓塞肺动脉组织中的表达

目的　探讨组织型纤溶酶原激活物 ( t PA)在急性肺血栓栓塞 ( PTE)肺动脉中的表达及意义。方法　 30只家兔随机分组。采用血栓阻塞法制备 PTE动物模型。取材栓塞 3、8和 2 4 h后动物栓塞部位的肺动脉和栓塞远端肺动脉 ;同时设实验对照组 ,取材正常肺动脉。应用免疫组化方法检测肺动脉组织内 t PA的抗原水平。结果　正常肺动脉极少见胞浆棕染的 t PA阳性细胞。栓塞 3h组的栓塞肺动脉和未栓塞肺动脉 t PA阳性细胞数与对照组比较差异没有显著性。栓塞 8h和 2 4 h组肺动脉残存的内皮细胞和平滑肌细胞内均可见明显的胞浆棕染的阳性细胞 ( P均 <0 .0 1)。结论　急性 PTE后可见到栓塞肺动脉 t PA表达增强 ,表明肺具有强大的纤溶潜力 ,这种内源性纤溶活性的增强有利于血栓的溶解     

组织型纤溶酶原激活物及纤溶酶原激活物抑制剂对系统性红斑狼疮的检测价值

<正>自身免疫介导并累及多个系统、临床表现起伏是系统性红斑狼疮(systemic lupus erythematosus,SLE)的显著特征,血液、造血系统受损较常见,其发病机制仍不十分清楚[1]。SLE可以引起全身多器官损害并常存在高凝状态,甚至发生血栓或     

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。     

组织型纤溶酶原激活物、尿激酶型纤溶酶原激活物在单侧输尿管梗阻大鼠不同阶段肾组织中的表达及意义

目的:建立单侧输尿管梗阻大鼠模型,观察组织型纤溶酶原激活物(t-PA)、尿激酶型纤溶酶原激活物(u-PA)在不同时间点肾组织中的表达情况,探讨其不同的表达与肾间质纤维化的关系。方法:实验于2006-05/2007-04在泸州医学院附属医院病理学实验室及传染免疫学实验室完成。72只清洁级雄性SD大鼠,随机分为3组,正常组24只,假手术组24只,模型组24只。各组大鼠于单侧输尿管结扎术后1,4,7,14d取肾组织进行病理分析,观察各组大鼠于单侧输尿管梗阻术后1,4,7,14d的肾小管损伤与肾间质纤维化情况,并采用免疫组织化学技术动态观察t-PA、u-PA在各组的表达情况。实验过程中对动物处置符合动物伦理学标准。结果:参加实验动物72只,中途共死亡5只,均及时补充,最后进入结果分析大鼠为72只。①模型组术后4d,肾脏组织即表现早期纤维化的病理改变,术后第7天,肾小管表现出明显损害,术后14d,肾间质纤维化表现明显。②假手术组较正常组各时间点t-PA、u-PA表达明显减少(P<0.05),模型组t-PA、u-PA在梗阻初期均随梗阻时间延长表达增多,术后第4天表达最多,以后随梗阻时间延长表达逐渐减少。结论:在输尿管梗阻早期,肾组织可能自身代偿分泌合成t-PA、u-PA,在一定程度下有利于延缓肾间质纤维化的进展,随着纤维化的发展,肾小管上皮细胞变性坏死,t-PA、u-PA分泌逐渐减少。     

组织型纤溶酶原激活物研究进展

组织型纤溶酶原激活物（ｔ－ＰＡ）对于维持机体内纤溶和凝血两个系统的平衡、防止血栓形成起着重要作用。本文着重从ｔ－ＰＡ分子的结构特征、生理作用机制、代谢调节以及血液中ｔ－ＰＡ浓度变化在临床上的意义等几个方面，综述了近年来ｔ－ＰＡ研究的新进展。     

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。     

重组组织型纤溶酶原激活剂与尿激酶治疗急性肺栓塞的对比研究

急性肺栓塞临床并不少见,病死率高,如果能及时诊断并给予溶栓治疗可明显降低病死率.溶栓治疗已成为急性肺栓塞治疗常规之一.溶栓药物以尿激酶(UK)应用比较广泛,也取得了较好的疗效,但有时会出现出血等并发症.重组组织型纤溶酶原激活剂(rt-PA)是新型溶栓剂,采用细胞重组DNA技术生产,不具有抗原性,其直接将纤溶酶原转变成纤溶酶,对纤维蛋白比UK更具有特异性,国内外均已开始用于急性肺栓塞的溶栓治疗.我们以我院呼吸内科收治的急性肺栓塞患者为研究对象,探讨rt-PA及UK在急性肺栓塞溶栓治疗中的应用价值.     

重组组织型纤溶酶原激活剂治疗下肢深静脉血栓的护理

介绍5例下肢深静脉血栓患者，经用重组组织型纤溶酶原激活剂rt—PA治疗，2周后阻塞血管均部分再通，临床症状显著改善。护理措施是：用药前心理护理，包括患者病情的安慰解释工作、药物治疗的效果和可能出现的副作用，解除患者的思想顾虑，配合治疗；用药时，注意担液局部温水湿敷，扭液针头要粗，前50mgrt-PA滴速要快；用药后主要观察患肢肿胀程度、皮肤温度、足背动脉搏动的变化以及全身皮肤、粘膜有无出血点，密切观察呼吸系统症状；治疗中，抬高患肢20～30°，患肢不可过热、过冷。     

表皮细胞中钙离子调节组织型纤溶酶原激活剂表达的机制

目的：探讨小鼠表皮角质形成细胞（KC）中，Ca^2 对组织型纤溶本科原激活剂（tissue plasminogen activator,tPA)表达的调节及其作用机制。方法：利用免疫细胞化学及RT-PCR等方法，定性，定量检测在不同浓度Ca^2 及异博定，放线菌素D作用下，tPA蛋白质或mRNA表达的变化情况。结果：与低Ca^2 浓度相比，高Ca^2 浓度下，表皮KC中tPA蛋白及mRNA的量均发生了非常显著的增加，而异博定及放线菌素D的加入，则可抑制高Ca^2 浓度的这一作用。结论：在小鼠表皮KC中，胞外高浓度Ca^2 可通过细胞膜上的电位依赖性离子通道进入胞内，在转录水平上调节tPA的表达。     

重组组织型纤溶酶激活剂治疗急性脑梗死的临床研究

【目的】观察重组组织型纤溶酶原激活剂（rt—PA）静脉溶栓治疗早期急性脑梗死的疗效和安全性。【方法】急性脑梗死84例（发病时间〈6h）随机分为溶栓组（＂-34）和对照组（n=50）。溶栓组用rt—PA0．9mg／kg,溶栓12h后给予皮下注射低分子肝素钙0．4mL,2次／d,连续应用7d;对照组不使用rt—PA,其他治疗均与溶栓组相同。于治疗前后评定临床神经功能缺损程度评分（NIHSS）和Barthel指数,监测纤维蛋白原（Fib）水平以及颅内出血情况。【结果】溶栓组治疗后24h、7d、1个月及3个月的NIHSs评分均明显低于对照组（P〈0．05）;两组患者治疗7d后Barthel指数开始明显升高,治疗后7d、1个月及3个月溶栓组的Bar—theI指数均明显高于对照组（P〈0．05）;溶栓组显效率和总有效率均高于对照组（x2=8．57,9．84;P〈0．01）;两组Fib水平治疗后12h明显降低（P〈O．05）,治疗后48h及72h两组Fib水平恢复至治疗前水平,两组间差异无显著性。两组死亡率及出血并发症发生率差异无显著性。【结论】急性脑梗死早期应用rt—PA静脉溶栓治疗安全有效。     

Effect of Thrombin and Incubation Time on Porcine Whole Blood Clot Elasticity and Recombinant Tissue Plasminogen Activator Susceptibility

Deep vein thrombosis is a major source of morbidity and mortality worldwide. Catheter-directed thrombolytics are the frontline approach for vessel recanalization, though fibrinolytic efficacy is limited for stiff, chronic thrombi. Although thrombin has been used in preclinical models to induce thrombosis, the effect on lytic susceptibility and clot stiffness is unknown. The goal of this study was to explore the effect of bovine thrombin concentration and incubation time on lytic susceptibility and stiffness of porcine whole blood clots in vitro. Porcine whole blood was allowed to coagulate at 37°C in glass pipets primed with 2.5 or 15 U/mL thrombin for 15 to 120 min. Lytic susceptibility to recombinant tissue plasminogen activator (rt-PA, alteplase) over a range of concentrations (3.15–107.00 µg/mL) was evaluated using percentage clot mass loss. The Young's moduli and degrees of retraction of the clots were estimated using ultrasound-based single-track-location shear wave elasticity and B-mode imaging, respectively. Percentage mass loss decreased and clot stiffness increased with the incubation period. Clots formed with 15 U/mL and incubated for 2 h exhibited properties similar to those of highly retracted clots: Young's modulus of 2.39 ± 0.36 kPa and percentage mass loss of 8.69 ± 2.72% when exposed to 3.15 µg/mL rt-PA. The histological differences between thrombin-induced porcine whole blood clots in vitro and thrombi in vivo are described.     

Intraosseous Administration of Tissue Plasminogen Activator on a Mobile Stroke Unit

Objective: Mobile stroke units offer improved time to administration of thrombolytics for ischemic stroke patients. Acquisition of intravenous (IV) access, however, can be challenging in the prehospital environment leading to treatment delays. Intraosseous (IO) access is commonly used in the prehospital setting for a variety of conditions and may serve as a viable means for tPA (tissue plasminogen activator) administration. Methods/Results: We describe 3 cases in which tPA was administered via IO access on a mobile stroke unit as part of the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services (BEST-MSU) trial. Conclusion: No adverse events were observed in the process of obtaining IO access or administering tPA.     

Emergency Physician Treatment of Acute Stroke with Recombinant Tissue Plasminogen Activator: A Retrospective Analysis

Stroke teams are advocated for the rapid treatment of patients who have acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA). An alternate model uses existing ED resources with specialist consultation as needed. OBJECTIVES: To evaluate the treatment of AIS with rt-PA in this alternate ED model. METHODS: A retrospective observational review was performed of consecutive patients with AIS treated with rt-PA at four hospitals affiliated with an emergency medicine residency. Emergency physicians (EPs) were directly responsible for the treatment of all patients according to predefined guidelines. Records were evaluated from the implementation of the guidelines through December 15, 1997. RESULTS: 37 patients with AIS received rt-PA. Mean age+/-SD was 63+/-16 years (range 22-87), with 25 (68%) male. Patients presented 67+/-29 minutes after stroke onset. After ED arrival, they were seen by the EP in 14+/-13 minutes, had CT in 46+/-22 minutes, and were treated in 97+/-35 minutes. Neurologist consultation occurred in the department for nine patients (24.3%), and by telephone for 14 (37.8%). Symptomatic intracerebral hemorrhage (ICH) occurred in four (10.8%, 95% CI = 0.8% to 20.8%). There were two deaths, neither associated with ICH. Neurologic outcome at discharge compared with presentation in survivors was normal for four patients (11.4%), improved for 16 (45.7%), unchanged for ten (28.6%), and worse for five (14.3%). CONCLUSIONS: In this analysis, EPs, with specialty consultation as required, successfully identified patients with AIS and delivered rt-PA with satisfactory outcomes. Important elements of this model include early patient identification, preestablished protocols, and rapid access to CT scanning and interpretation.     

重组组织型纤溶酶原激活剂与尿激酶溶栓治疗急性心肌梗死的疗效比较

目的：观察小剂量（50mg)重组织型纤维酶原激活剂（rt-PA)与尿激酶（UK）溶栓治疗急性心肌梗死（AMI）的疗效及安全性,方法：将116例AMI患随机分为rt-PA组和UK组,分别应用rt-PA和UK溶栓治疗,结果：冠状动脉（冠脉）总再通率分别rt-PA组80．65％和UK组为51．85％,患在发病后6h内治疗,冠脉再通率分别为rt-PA组91．18％和UK组67．86％,前明显高于后,两组比较均有显差异（P＜0．01）,5wk住院病死率分别为rt-PA组6．5％和UK组11．1％,结论：小剂量（50mg)rt-PA用于AMI溶栓治疗的临床疗效明显优于UK,血管再通率高,尤其在发病后6h内进行治疗效果更佳.rt-PA溶栓并发症少,可降低闰 率,是一种安全有效的溶栓剂.     

Intravenous Tissue Plasminogen Activator for Stroke: A Review of the ECASS III Results in Relation to Prior Clinical Trials

Background: Intravenous tissue plasminogen activator (IV tPA) is currently approved by the Food and Drug Administration for use in acute ischemic stroke patients up to 3 h from symptom onset, based primarily on the National Institute of Neurological Disorders and Stroke tPA trials published in 1995. The most recent trial published with IV tPA in stroke (European Cooperative Acute Stroke Study [ECASS] III) studied patients between 3 and 4.5 h from symptom onset and found a benefit to treatment in the rate of favorable outcome when compared to placebo, with no difference in mortality. Objectives: To examine the patient selection criteria and primary outcomes in ECASS III as compared to prior clinical trials and the current practice in the United States to determine how these new data could be applied to clinical practice. Discussion: With the exception of the longer time from symptom onset to treatment, ECASS III used more restrictive patient selection criteria than is the current practice in the United States to determine patient eligibility for IV tPA. Conclusions: Based on the combined data from all trials, the benefits of thrombolysis with IV tPA for acute ischemic stroke outweigh the risks of treatment for selected patients up to 4.5 h from symptom onset. It is already known that thrombolysis is not beneficial for all stroke patients and strict criteria should be applied before treatment. As time from symptom onset increases, the need for careful patient selection likely also increases.     

急性脑梗死静脉溶栓治疗的难点与对策

本文指出按照国际指南以重组组织型纤溶酶原激活剂（r-tPA）进行规范静脉溶栓治疗急性脑梗死的重要性；提出了临床实践中常见的5方面问题：接受溶栓治疗的急性脑梗死患者较少、r-tPA的价格限制了临床应用、中国人r-tPA用量尚待摸索、溶栓疗效不理想以及中医药参与溶栓治疗有限，并对每一问题提出应对措施。对中医药干预超早期脑梗死溶栓治疗提出自己的想法。