人血清白蛋白修饰的尿激酶与天然尿激酶的家兔体内过程比较

家兔静注人血清白蛋白修饰的尿激酶(MUK)和天然尿激酶(NUK)40000IU后,MUK 的体内过程符合零级速率过程,NUK 则符合一级速率过程,血纤溶活性 MUK 持续100min,而 NUK 仅20～25min。在“功能性”去除肝肾的家兔,NUK 血浓度半衰期延长3～4倍,而 MUK 血浓度下降与正常家兔相似。MUK 及 NUK 在去除纤溶抑制物的优球蛋白成份中纤溶活性相似,但在血浆中 NUK 仅存24～35%的纤溶活性,MUK 则保留了64～85%的纤溶活性。提示肝肾的摄取、代谢和消除能力降低及对血浆纤溶抑制物抵抗力增强,是 MUK 血纤溶活性长时间维持高水平的主要原因。     

尿激酶对脑梗死特异性烯醇化酶的影响及其临床意义

目的：探讨尿激酶与急性脑梗死（ACI）患者特异性烯醇化酶（NSE）的关系。方法：该实验采用酶联免疫吸附法（EusA）测定脑梗死常规治疗组、尿激酶治疗组血清NSE水平。结果：尿激酶组NSE值显著低于ACI常规治疗组。结论：尿激酶能降低血清酶活性，使已形成的纤维蛋白水解，从而缩小梗死灶体积，改善脑缺血、缺氧，从而起到保护脑细胞的作用。     

超早期颅骨锥孔尿激酶冲洗治疗脑出血102例

目的总结超早期颅骨锥孔尿激酶冲洗治疗脑出血的经验与教训。方法对102例发病在6h内的脑出血病人,采用颅骨锥孔置管后,用尿激酶冲洗引流。结果恢复正常29例(28.5%),轻残36例(35.3%),重残20例(19.6%),植物生存5例(4.9%),死亡12例(11.8%)。住院治疗期间无一例复发和颅内感染。结论超早期颅骨锥孔尿激酶冲洗治疗脑出血,血肿溶解迅速,引流效果好,且不会破坏患者凝血机制。     

^1H-magnetic resonance spectroscopy screening for animals with acute cerebral infraction suitable forthrombolytic therapy

BACKGROUND: As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy (1H-MRS) may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke. OBJECTIVE: To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability. DESIGN: Randomly controlled animal study. SETTINGS: Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS: Eleven healthy adult Sprague-Dawley (SD) rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology [SCXK (e) 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS: The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group (n =6) and 60-minute self-thrombo-embolism group (n =5). Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid (NAA)/phosphocreatine (PCr) + creatine (Cr), choline phosphate (Cho)/PCr+Cr and lactic acid (Lac)/PCr+Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope. MAIN OUTCOME MEASURES: ① Metabolic changes of NAA/PCr+Cr, Cho/PCr+Cr and Lac/PCr+Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue. RESULTS: Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests : In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy (0.252±0.01, 0.603±0.01, P < 0.01). Lac/(PCr+Cr) ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis (P < 0.01). The NAA/ (PCr+Cr) ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis (0.922±0.16, 1.196±0.01, P < 0.05). In 60-minute self-thrombo-embolism group, the Lac/(PCr+Cr) ratio was higher at 3 hours after thrombolysis than that before thrombolysis (0.846±0.12, 0.601±0.11, P < 0.05) and the NAA/(PCr+Cr) decreased at 3 hours after the embolism. Fluctuation of NAA/ (PCr+Cr) ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image: T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA > 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations: Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateral part of corpus striatum. CONCLUSION: ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.     

小剂量尿激酶溶栓治疗老年高龄急性心肌梗死65例临床观察

目的尝试用小剂量尿激酶治疗老年高龄急性心肌梗死,旨在使老年高龄患者亦从溶栓治疗中获益.方法采用WHO关于急性心肌梗死(AMI)的诊断标准,收治老年高龄患者65例.随机分为两组,溶栓组31例,给予小剂量尿激酶(50×104U)30min 静脉滴入;并与非溶栓组34例对照观察.结果溶栓组冠脉再通率、五周病死率、休克、心衰分别为54.8%、6.4%、3.2%、9.7%;而对照组分别为14.7%、23.5%、26.5%:41.2%,有明显差异(P<0.01).结论有条件的基层医院依然有可能实施小剂量尿激酶对老年高龄患者的溶栓治疗,且可挽救更多老年高龄患者的生命.     

三维重建单(双)靶点定向置管引流术治疗高血压壳核出血

目的回顾性分析三维重建单(双)靶点定向置管引流术治疗高血压壳核出血的疗效,验证该方法的有效性和可行性。方法将133例壳核脑出血病人的CT定位扫描资料输入计算机工作站,对血肿进行三维重建,根据血肿量的大小和形状设计1～2个靶点和引流管路径。应用立体定向技术将引流管(外径5mm,内径3mm)送至颅内预定靶点,术中应用10ml注射器轻柔抽吸血肿液化部分,术后将尿激酶(1～2万IU)注入血肿腔内,夹闭引流管2h后自然引流,每12h重复1次。复查CT证实剩余血肿量为最初的10%~15%时拔除引流管。结果平均置管1.5 d(1～3d),平均血肿排空率92.8%。术后1个月病死率6.0%,远期随访(平均22个月)病死率11.3%,优良率74.4%。结论该方法治疗高血压壳核脑出血,血肿排空较彻底,疗效可靠,尤其适用于血肿量较大(>25ml)且形态不规则的颅内血肿。     

应用结合于内皮细胞的尿激酶预防血栓形成

提纯出受损伤内皮细胞的特异性抗原，再用免疫学方法制得相应抗体，并把它与尿激酶形成结合物。在人工造成血管内皮细胞损伤的动物中，分别用尿激酶结合物、单纯特异性抗体处理，各组动物处死后进行形态学观察。结果显示：在未用尿激酶结合物处理的动物血管内和使用结合物处理的血管内，血栓形成的程度有明显的差别，前者明显，后者轻微。这种方法既能预防血栓形成，又不会产生继发性出血的危险。     

Targeted Thrombolytic Liposomes

Becauseofvariousthrombolyticagentsnowavailableassociatedwithlowthrombolyticspecificity ,largedoserequiredforclinicaltreatment,andperplexingsideeffectofhemorrhage ,westudiedthethrombus targetedliposomeswhichhavespecificaffinitytoactivatedplatelets .WithtetrapeptideRGDSasthehomingdevice ,theobtainedliposomescanspecifi callyrecognizethereceptorGPIIb IIIaoftheactivatedplateletsinthrombus ,bywhichthrombustargetabilityisachieved .Thefollowingpartsareincludedinthestudy .Eggphosphatidylcholine (E…     

微创治疗迟发性脑内血肿(附78例报告)

目的：评价微创治疗迟发性脑内血肿的疗效。方法：采取锥颅穿刺置管 尿激酶灌注引流方法，回顾分析78例迟发脑内血肿的临床资料。结果：78例迟发脑内血肿经微创治疗后存活71例，死亡5例，总死亡率6％。格拉斯哥昏迷指数(GCS)、年龄、瞳孔变化、血肿大小、脑挫伤程度及并发症等6项指标可影响治疗效果。结论：迟发性脑内血肿采取微创治疗具有安全性、少创、经济、恢复时间短、并发症少、死亡率低等优点。是一种有效可靠的方法。     

Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis

Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and urokinase type plasminogen (uPA) correlated with the development and metastasis of cancers. To investigate the role of HGF/c-met signaling on metastasis in cancer cells stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580) on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of PD98059 decreased HGF-mediated phosphorylation of extracellular receptor kinase (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and MMP-9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF-stimulated ERK phosphorylation, uPA secretion and expression of MMPs. SB203580 also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in the PD98059-pretreated cells. These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway. This revised version was published online in July 2006 with corrections to the Cover Date.