尿激酶动脉溶栓与重组组织型纤溶酶原激活剂静脉溶栓治疗缺血性卒中的疗效比较

目的评价选择性动脉溶栓治疗急性脑梗死的疗效和安全性。方法回顾性分析发病6 h内的急性脑梗死患者43例的临床资料,其中动脉溶栓组31例,静脉溶栓组12例。动脉溶栓组患者在发病6 h内经DSA证实为颅内血管闭塞,并进行超选择性动脉溶栓治疗(尿激酶总量<75万U);静脉溶栓组患者于发病3 h内接受重组组织型纤溶酶原激活剂(rt-PA)的溶栓治疗(0.9 mg/kg)。观察两组的血管再通情况,于治疗后14d、90d及6个月,随访两组患者的美国国立卫生研究院卒中量表(NIHSS)评分、Bahel指数等情况。结果①动脉溶栓后,21例(67.74%)患者的临床症状完全恢复正常或有明显好转,术后14d的NIHSS评分(12±7)低于术前评分(15±4),差异有统计学性意义,P<0.01。②动脉溶栓后18例完全再通、7例部分再通,6例未通。动脉溶栓术后90 d疗效比较,完全再通组优于未通组;术后6个月疗效比较,完全再通组优于未通组,部分再通组优于未通组,差异均有统计学意义。③不同牛津郡社区卒中项目(OCSP)分型患者经动脉溶栓后,术后14d的NIHSS评分均低于溶栓前的NIHSS评分,术后90d的NIHSS评分均低于溶栓前的和溶栓后14d的NIHSS评分,差异有统计学意义,P<0.05。④动脉溶栓组的脑出血发生率、溶栓后14 d和90 d的NIHSS评分与发病3 h内静脉溶栓组比较,差异无统计学意义,P>0.05。结论时问窗内动脉溶栓治疗能够明显提高闭塞血管的再通率,改善患者急性期临床症状和远期预后。在发病6 h后动脉溶栓组的近期疗效和远期预后均与静脉溶栓组相当。

影响重组组织型纤溶酶原激活剂治疗卒中患者临床预后的相关因素

本文通过对大量文献的阅读,就可能影响重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗缺血性脑卒中患者临床预后的因素作一综述,rt-PA溶栓虽能改善患者临床预后,但受许多因素的影响,如年龄、性别、起病至溶栓治疗时间(OTT)、高血压病、溶栓时血压、糖尿病、溶栓时高血糖、房颤、卒中严重程度、抗血小板药物等,应在临床应用时充分考虑影响疗效的各种因素,进行全面评估。

重组组织型纤溶酶原激活剂与直接冠状动脉内支架术治疗心肌梗死的疗效比较

目的 比较小剂量重组组织型纤溶酶原激活剂 (rt PA)与直接冠状动脉 (冠脉 )支架术治疗急性心肌梗死 (AMI)的临床疗效。方法 131例患者接受小剂量rt PA 5 0mg静脉溶栓治疗 (溶栓组 ) ,130例患者接受梗死相关动脉 (IRA)直接冠脉支架术 (支架组 ) ,比较两组之间患者的临床治疗效果。结果 小剂量rt PA溶栓治疗组IRA再通率为 81 7%,直接冠脉支架组再通率为 98 5 %,两组差异有显著性 (P <0 0 0 0 0 1)。溶栓组再发心肌梗死、需要择期冠脉支架术明显高于支架组 (分别为7 6 %比 1 5 %,P <0 0 5 ;2 0 6 %比 0 ,P <0 0 0 0 1)。溶栓组住院期间左心室射血分数明显低于支架组[(5 5 6± 13 4 ) %比 (6 5 8± 9 2 ) %,P <0 0 0 0 1]。溶栓组平均住院天数也明显多于支架组 (16± 7比11± 4,P <0 0 0 0 1)。溶栓组住院病死率高于支架组 ,但差异无显著性 (6 1%比 3 1%,P >0 0 5 )。结论 与小剂量rt PA静脉溶栓比较 ,直接冠脉支架术可明显增加IRA的再通率 ,更好地保护心功能 ,并缩短患者的住院时间。

冠状动脉造影和PTCA术对冠心病纤溶活性的影响

目的 :观察选择性冠状动脉造影 (SCA)和 PTCA对冠心病纤溶活性的影响。方法 :对接受 SCA的 45例患者和 PTCA术后 19例患者的血浆组织型纤溶酶原激活物抗原 (t- PA:Ag)、纤溶酶原激活物抑制物 (PAI1 )和纤维蛋白二聚体 (DD)含量进行动态观测。结果 :1SCA后 SCA正常组、稳定型和不稳定型心绞痛组 t- PA:Ag含量均显著升高 (P<0 .0 1) ,前者 2 4h,后者 72 h内恢复 ;活性无显著变化 ;t- PA:Ag升高程度以 SCA正常组最明显 ,显著高于稳定和不稳定型心绞痛组。 2 PTCA术后 t- PA:Ag,DD含量和 PAI1 活性均显著升高 ,PAI1 活性 3d内、t- PA :Ag 7d内恢复 ,DD含量 7d内仍高于术前。结论 :冠心病患者有 t- PA:Ag储存和释放障碍 ,SCA和 PTCA术后纤溶活性有增加趋势 ,可能与术前、术后抗血小板药物及术中、术后肝素应用有关。

经胸廓内动脉置泵对急性心肌缺血犬t-PA和PAI的影响

目的 通过建立经胸廓内动脉置泵治疗犬急性心肌缺血的动物模型 ,观察介入组和对照组组织型纤溶酶原激活物及其抑制物 ( t PA、PAI)的变化。方法 6 0条健康杂种犬 ,随机分为介入组和对照组 ,每组 30条。在静脉麻醉下开胸 ,结扎左冠状动脉前降支 ,建立急性心肌缺血动物模型。介入组分离胸廓内动脉后远端结扎 ,在近端置管 ,外接输液加压泵 ,通过胸廓内动脉加压滴注硝酸甘油 ;对照组通过外周静脉滴注硝酸甘油。于冠状动脉结扎前、结扎后 0 .5 h、以及给予硝酸甘油 2 h和 6 h后股静脉采血测定 t PA和 PAI。结果 在冠状动脉结扎后 0 .5 h两组 t PA均升高 ,对照组在 2 h和 6 h逐渐下降 ,而介入组无明显变化 ;两组在结扎后 6 h差异有统计学意义 ( P<0 .0 5 )。冠状动脉结扎后两组 PAI逐渐上升 ,对照组在结扎后 6 h最高 ,而介入组在结扎后 2 h最高 ;两组 PAI在结扎后 6 h差异有统计学意义 ( P<0 .0 5 )。结论 经胸廓内动脉置泵介入治疗犬急性心肌缺血可促进血管内皮释放 t PA、抑制 PAI分泌 。

实验性肺血栓栓塞症后凝血纤溶系统及肺血管内皮功能变化的临床意义

目的 探讨实验性兔肺血栓栓塞症 (PTE)后凝血纤溶系统、肺血管内皮功能的变化及其临床意义 ,了解尿激酶对凝血纤溶系统及肺血管内皮功能的影响。方法 2 4只雄性新西兰大耳白兔随机分为正常对照组、单纯栓塞组及尿激酶组 ,每组 8只。单纯栓塞组及尿激酶组经兔股静脉注入自体血凝块制备兔PTE模型。尿激酶组用尿激酶治疗动态观察尿激酶治疗前后兔凝血纤溶系统活性和血浆中内皮素 1(ET 1)、一氧化氮 (NO)、血管性血友病因子 (vWF)的变化。结果 解剖肺脏栓塞部位肉眼观 ,见肺表面点片状出血灶 ;镜下肺动脉血管内可见注入的血凝块与继发的血栓形成 ,肺泡周围有大量炎性细胞浸润 ,肺泡和间质内有局灶出血。肺栓塞后血D 二聚体 (D dimer)、ET 1、vWF水平明显增高 ,而组织型纤溶酶原激活剂 (t PA)、NO、抗凝血酶Ⅲ (AT Ⅲ )水平明显下降 (P <0 0 5 )。PTE兔经尿激酶治疗后肺脏病理改变减轻 ,D dimer水平在栓塞后 1及 2h高于栓塞前 (P <0 0 5 ) ,4h后降至栓塞前水平 ;t PA、NO及AT Ⅲ在肺栓塞后低于栓塞前 (P <0 0 5 ) ;ET 1在栓塞后 2h高于栓塞前(P <0 0 5 ) ,4h降至栓塞前水平。结论 PTE对体内凝血纤溶系统及肺血管内皮功能均有重要影响。

氧化修饰低密度脂蛋白对内皮细胞功能的影响

目的观察氧化修饰低密度脂蛋白(ox-LDL)对内皮细胞NO/ET-1、t-PA/PAI-1合成、细胞表面细胞间黏附分子-1(ICAM-1)表达的影响。方法采用培养的人脐静脉内皮细胞(HUVECs),在分别加入不同浓度ox-LDL(50、100、150、200 mg/L)孵育24 h后,观察培养液中NO、ET-1、t-PA、PAI-1水平及细胞表面ICAM-1的表达。结果ox-LDL可显著抑制NO、t-PA的合成,ox-LDL还可明显增加ET-1、PAI-1的分泌及诱导细胞表面ICAM-1的表达。结论ox-LDL对内皮细胞具有明显的细胞毒作用,它对NO/ET-1、t-PA/PAI-1及ICAM-1表达的影响可能是其致动脉粥样硬化发生的重要机制之一。

An Experimental Study of Pathogenesis of Steroid-induced Avascular Necrosis of Femoral Head

Objective: To explore the pathogenesis of avascular necrosis of femoral head(ANFH) and search an effective method for clinical practice. Methods: Twenty-four Japanese rabbitswere divided into 2 groups of models and controls. ANFH models were produced byintramuscular-injection of large dosage of steroid to rabbits for 8 weeks. From the 4th, 8th and12th week after production of models, 2 rabbits of each group were sacrificed to observe thestructure of femoral head through light microscope and scanning electron microscope. The contents ofNitric Oxide (NO), tissue-type plasminogen activator (t-PA) and -plasminogen activator inhibitor(PAI) in plasma of the 4 rabbits in each group were estimated at the same time. Results: Comparedwith control group, the rabbits of model group exhibited many differences: such as osteoporosis offemoral head, the presence of more bone lacuna and fat cell through light microscope observing; thebroken and sunk bone trabecula, the loosen and broken collagen fibers on the surface of bone matrixthrough scanning electron microscope observing. Compared with control group, the Concentration ofNO and t-PA in plasma of the model rabbits decreased obviously, but the Concentration of the PAIincreased obviously. Conclusion: The steroid-induced ANFH might be related to the lower level of NOand the descent of fibrinolytic activity.

Clinical Research on the Changes of Plasma TFPI and uPA System in Malignant Tumor

Objective: To investigate the expression levels and significance of TFPI, uPA, uPAR and PAI in malignant patients. Methods: The levels of TFPI, uPA and uPAR were measured by using ELISA and the level of PAI was determined by method of chromogenic substrates in 44 patients with malignant solid tumors (group A1) and 30 patients with acute leukemia (AL, group A2). Results: The levels of TFPI, uPA, and uPAR in group A1 were higher than those in normal control group (group B). TFPI, uPAR levels in group A2 were higher than those in group B, while the level of PAI in group A2 was lower than that in group B. Among the groups, TFPI was increased in the combined infection group; PAI decreased in the hemorrhage group; TFPI, uPA, uPAR and PAI increased in relapsing and metastasis group; TFPI decreased in one-week dead group, while uPA and uPAR increased. Conclusion: The patients with malignant solid tumor and AL had different anticoagulation or fibrinolysis states. TFPI, uPA, Upar and PAI can be used to evaluate the disease condition and the prognosis.

The Role of Tissue-type Plasminogen Activator in Rat Corpus Luteum

It is here reported for the first time that luteal cells are capable of secreting plasminogen activators(PA),(both tissue-type,tPA,and urokinase-type,uPA),and plasminogen activator inhibitor type-1(PAl-1).Using organ culture model,we have demonstrated that tPA,but not uPA,showed markedchange during luteolytic period in rat corpus luteum.A great amount oftPA was secreted in corpusluteum on D 14 and D 17 while very low level of tPA activity was detected before D 12.Correspondingly,the progesterone production in the corpus luteum increased gradually in a time-dependent manner from D 1 to D 12 but dropped abruptly to a very low level on D 14.Additionof exogenous tPA to the CL culture caused considerable decrease in progesterone secretion whileinclusion of purified monoclone tPA antibodies in the culture augmented progesterone productionof CL.It is therefore suggested that tPA may play an important role in luteolytic process.

Clinical significance of plasma tissue factor pathway and urokinase-type plasminogen activator system in cancer patients

OBJECTIVE: To evaluate variations in the plasma tissue factor (TF) and urokinase type plasminogen activator (u-PA) system and their relationship with clinical cancer type, pathological classification and metastatic status in cancer patients. METHODS: Plasma levels of TF and its inhibitor (TFPI), as well as u-PA and its receptor (u-PAR) were measured using ELISA in 76 patients with malignant tumors and 24 patients with benign tumors. RESULTS: Plasma levels of TF and u-PAR in the malignant tumor group were significantly higher than those of the benign tumor group and the normal control. U-PA and u-PAR increased significantly in patients with esophageal and gastric cancer. However, most of these parameters except TFPI did not vary according to pathological classification. A significant elevation was evident in patients with local infiltration, lymph node involvement and distal metastasis, while u-PAR only increased in the latter two categories. CONCLUSIONS: Both the TF and u-PA systems are activated in cancer patients. U-PA and its receptor might prove to be a clinically useful marker for disease progression.

Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol

Objective To investigate the mechanism of prolonged uterine hemorrhage after terminating early pregnancy by mifepristone plus misoprostol.Methods Forty-five decidua specimens were obtained from 45 pregnant women with amenorrhea of 6-7 week duration. Fifteen women were treated with mifepristone and 15 were treated with mifepristone plus misoprostol. The remaining 15 served as controls. The tPA and PAI-1 mRNA levels were estimated by reverse transcription-polymerase chain reaction. Chromogenic assay and enzyme-linked immunosorbent assay were used to detect tPA activity and PAI-1 protein level in decidua. Results The activities of tPA in the mifepristone plus misoprostol group and in the mifepristone group were 46.91±20.74?IU/mg*protein and 64.25±35.81?IU/mg*protein respectively, lower than those in the normal decidua group (99.76±58.61?IU/mg*protein, P<0.05). tPA mRNA levels in the mifepristone plus misoprostol group were the highest (1.43±0.39) among the groups. In the mifepristone group, tPA mRNA level (0.90±0.16) was not significantly different from that in the normal decidua group (0.94±0.17). The protein and mRNA expression levels of PAI-1 were not significantly different among the three groups (P>0.05).Conclusions Mifepristone plus misoprostol decreased tPA activity in human early decidua by post-transcription pathways, which may influence decidua shedding, endometrial angiogenesis, endometrial remodeling, and cause prolonged uterine hemorrhage after drug abortion.