疏血通注射液对2型糖尿病脑梗死大鼠血浆纤溶酶原激活物和抑制剂含量及其脑组织中mRNA表达的影响

目的探讨疏血通注射液对2型糖尿病脑梗死大鼠血浆中纤溶酶原激活物(t-PA)和抑制剂(PAI-I)含量及其脑组织mRNA表达的影响。方法建立大鼠糖尿病模型及大鼠糖尿病脑梗死模型,尾静脉注射疏血通注射液,大鼠眼眶静脉取血,检测t-PA和PAI-I含量,同时快速分离缺血侧脑组织,RT-PCR检测t-PA、PAI-I的基因mR-NA表达。结果疏血通注射液能提高t-PA的含量(P<0.01),降低PAI-I含量(P<0.01),提高t-PA、基因mRNA表达(P<0.01),降低PAI-I的基因mRNA表达(P<0.01)。结论疏血通注射液通过改善血浆和脑组织纤溶功能,对糖尿病脑梗死起到一定的治疗作用。     

光裸方格星虫纤溶酶对FeCl3诱导大鼠颈动脉血栓的抗栓作用研究

目的 研究光裸方格星虫纤溶酶（fibrinolytic enzyme from Sipunculus nudus,SNFE）对FeCl₃诱导大鼠颈动脉血栓的抗栓作用。方法 SD大鼠随机分为假手术组、模型组、阿司匹林组（100 mg·kg^-1）和SNFE高、低剂量组（5 000,2 500 IU·kg^-1）,连续灌胃给药14 d后,以30% FeCl₃诱导颈动脉血栓。成栓1 h后腹主动脉取血,测定凝血4项、组织纤溶酶原激活物（tissue-type plasminogen activator,t-PA）及I型纤溶酶原激活物抑制因子（plasminogen activator inhibitor-I,PAI-I）;称量各组血栓的湿重和干重,计算血栓形成抑制率,截取血栓环,进行HE染色。结果 与假手术组比较,模型组凝血酶原时间（prothrombin time,PT）、凝血酶时间（thrombin time,TT）明显缩短,纤维蛋白原（fibrinogen,FIB）含量明显增加（P<0.05或P<0.01）;与模型组相比,SNFE高剂量组PT、活化部分凝血酶时间显著延长,FIB含量减少（P<0.05或P<0.01）,低剂量组各项指标有改善趋势。与假手术组比较,模型组t-PA和t-PA/PAI-I明显减少（P<0.01）,PAI-I无明显差异;与模型组比较,SNFE高、低剂量组的t-PA及高剂量组的t-PA/PAI-I显著增加（P<0.05或P<0.01）,PAI-I无明显差异。与模型组比较,SNFE各剂量组的血栓干重和湿重均降低,SNFE高剂量组的干、湿重分别抑制56.86%和41.67%,低剂量组的干、湿重分别抑制21.57%和11.90%。模型组血管腔内有致密血栓,SNFE低剂量组血栓较模型组少,阿司匹林组及高剂量组无明显血栓块。结论 方格星虫纤溶酶可通过影响凝血系统和纤溶系统抑制FeCl₃诱导的大鼠颈总动脉血栓的形成。     

贝那普利对急性冠状动脉综合征患者凝血及纤溶系统的影响

目的探讨血管紧张素转换酶抑制剂对凝血及纤溶系统的影响。方法急性冠状动脉综合征患者48例,随机分为对照组(16例)和贝那普利组(32例),对照组按临床常规处理,贝那普利组在此基础上加用贝那普利10mg/d,分别于入院后即刻和第3天采血测激活的凝血时间(ACT)和血浆组织型纤溶酶原激活剂(t-PA)及其抑制物(PAI-I)。结果治疗前后及组间比较ACT均无显著变化;两组t-PA活性治疗后均比治疗前明显升高,而PAI-I活性明显降低(均P<0.05及<0.01),组间比较贝那普利组升高及降低的幅度显著高于对照组(P<0.01)。结论贝那普利对急性冠状动脉综合征患者的凝血系统无明显影响,但可使t-PA活性增高而PAI-I活性降低。     

氟伐他汀对纤溶系统的影响

目的：探讨氟伐他汀对纤溶系统的影响。方法：选用高脂血症患者,给予氟伐他汀治疗,测定服药前后血脂、血浆中纤溶酶原激活剂（t-PA)及纤溶酶原激活物抑制剂－1（PAI－1）含量,并与正常人作对照。结果：治疗前高脂血症患者的血浆t-PA含量明显低于正常人,而血浆PAI－1含量明显高于正常人,经降脂治疗后血浆t-PA含量上升,而血浆PAI－1含量下降,接近正常。结论：氟伐他汀可以明显降低高脂血症患者的血脂水平,并且具有一定的改善纤溶系统功能的作用。     

水蛭联合全蝎冻干粉对对大鼠颈动脉血栓形成及APTT、PT、TT、FIB水平的影响

摘要：目的 探讨水蛭联合全蝎冻干粉对大鼠颈动脉血栓形成的影响。方法 采用三氯化铁诱导颈动脉血栓形成,实验分6组,即假手术组、模型组、水蛭冻干粉组（水蛭组）、全蝎冻干粉组（全蝎组）、水蛭+全蝎半剂量组（半剂量组）、水蛭+全蝎全剂量组（全剂量组）,每组6只。末次给药后计算两侧颈总动脉血栓形成抑制率。采用血小板聚集及凝血因子分析仪测定活化部分凝血活酶时间（activated partial thromboplastin time,APTT）、血浆凝血酶原时间（prothrombintime,PT）、血浆纤维蛋白原（fibrinogen,FIB）、和凝血酶原时间（thrombin time,TT）水平。采用ELSIA检测血浆组织纤溶酶原激活物（tissue-type plasminogen activator,t-PA）、I型纤溶酶原激活物抑制因子（plasminogen activatorinhibitor-I,PAI-I）。HE染色观察各组血栓形成情况。结果 与模型组相比,水蛭组、全蝎组、半剂量组和全剂量组中血栓湿重和干重均降低,全剂量组抑制血栓形成效果最佳。与假手术组相比,模型组APTT、PT、TT缩短,FIB含量增加,t-PA水平下降;与模型组相比,给药各剂量组中APTT、PT、TT时间延长,FIB含量减少,t-PA水平增加。PAI-I在各组中无明显差异。模型组血管内均可见大量血栓,水蛭组、全蝎组和半剂量组血栓明显减少,全剂量组几乎没有明显血栓。结论 水蛭联合全蝎冻干粉通过影响凝血功能和纤溶系统抑制大鼠颈动脉血栓形成。     

苯扎贝特对老年糖尿病患者餐后三酰甘油、血管活性因子及血管内皮功能的影响

目的观察苯扎贝特对老年糖尿病患者餐后三酰甘油(TG)、血管活性因子及血管内皮功能的影响。方法 45例老年糖尿病患者苯扎贝特治疗前后均行6 h脂肪餐试验,观测血清TG、一氧化氮(NO)、内皮素-1(ET-1)、纤溶酶原激活物抑制剂-1(PAI-1)、组织型纤溶酶原激活物(t-PA)等血管活性因子的动态变化,采用高分辨超声检测空腹颈动脉内中膜厚度(C-IMT)及脂餐前后血管内皮依赖性舒张功能(FMD)。结果老年糖尿病患者治疗后餐前、餐后2 h、4 h及6 h时血清TG水平明显低于治疗前(P<0.05)。餐前、餐后2、4、6 h血清NO、t-PA表达水平明显高于治疗前(P<0.05),而血清ET-1、PAI-I表达水平明显低于治疗前(P<0.05)。C-IMT及ΔFMD明显低于治疗前(P<0.05),餐前、餐后4 h FMD明显高于治疗前(P<0.05)。结论苯扎贝特可降低老年糖尿病患者餐后高TG血症,改善血管活性因子及血管内皮功能。     

卡托普利对大鼠t-PA和PAI-1活性的作用

目的评价卡托普利对大鼠血浆t-PA和PAI-1活性水平的影响。方法给大鼠应用三种剂量的卡托普利,观察其对大鼠血浆t-PA和PAI-1活性水平的作用。结果卡托普利治疗后使大鼠血浆t-PA活性升高,PAI-1活性及PAI-1/t-PA活性比值显著降低,这种作用呈某种程度的剂量依赖性。结论卡托普利能增强大鼠纤溶系统的活性,这种作用呈某种程度的剂量依赖性。     

The role of platelets in cardiovascular disease: Molecular mechanisms

探讨水蛭联合全蝎冻干粉对大鼠颈动脉血栓形成的影响。

采用三氯化铁诱导颈动脉血栓形成,实验分6组,即假手术组、模型组、水蛭冻干粉组(水蛭组)、全蝎冻干粉组(全蝎组)、水蛭+全蝎半剂量组(半剂量组)、水蛭+全蝎全剂量组(全剂量组),每组6只大鼠。末次给药后计算两侧颈总动脉血栓形成抑制率。采用血小板聚集及凝血因子分析仪测定活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、血浆凝血酶原时间(prothrombin time,PT)、血浆纤维蛋白原(fibrinogen,FIB)和凝血酶原时间(thrombin time,TT)。采用ELSIA检测血浆组织纤溶酶原激活物(tissue-type plasminogen activator,t-PA)、I型纤溶酶原激活物抑制因子(plasminogen activator inhibitor-I,PAI-I)。HE染色观察各组血栓形成情况。

与模型组相比,水蛭组、全蝎组、半剂量组和全剂量组中血栓湿重和干重均降低,全剂量组抑制血栓形成效果最佳。与假手术组相比,模型组APTT、PT、TT缩短,FIB含量增加,t-PA水平下降;与模型组相比,各给药组中APTT、PT、TT时间延长,FIB含量减少,t-PA水平增加。PAI-I在各组中差异无统计学意义。模型组血管内均可见大量血栓。与模型组相比,水蛭组、全蝎组和半剂量组血栓明显减少,全剂量组几乎没有明显血栓。

水蛭联合全蝎冻干粉通过影响凝血功能和纤溶系统抑制大鼠颈动脉血栓形成。

     

糖尿病视网膜病变时t-PA和PAI-1活性变化的临床意义

目的探讨糖尿病视网膜病变(DR)时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(PAT-1)的变化规律及临床意义.方法t-PA和PAI-1活性采用发色底物法.结果DR组血浆t-PA低于单纯糖尿病组(P＜0.05)和对照组(P＜0.01),PAI-1高于单纯糖尿病组(P＜0.05)和对照组(P＜0.01),单纯糖尿病组t-PA低于对照组(P＜0.05)及PAI-1高于对照组(P＜0.05).结论DR有纤溶功能损害,检测糖尿病患者血浆t-PA和PAI-1活性水平,对DR预防和治疗具有一定的临床意义.     

清脑通络胶囊对急性脑梗塞患者血浆凝血及纤溶指标的影响

目的观察清脑通络胶囊对急性脑梗塞患者血浆D-二聚体、纤维蛋白溶酶原（PLG）、抗凝血酶-Ⅲ（AT-Ⅲ）含量的影响,以分析其作用机理。方法将64例急性脑梗塞患者随机分为两组,治疗组（清脑通络胶囊＋常规药物治疗组33例）,对照组（常规药物治疗组31例）。观察两组患者治疗前后D-二聚体、PLG、AT-Ⅲ含量的变化。结果治疗组治疗后血浆AT-Ⅲ含量明显升高,与对照组比较,差异有显著性意义（P〈0.05）;D-二聚体、PLG含量明显降低,但与对照组间比较无统计学差异（P〈0.05）。结论清脑通络胶囊可以提高急性脑梗塞患者血浆AT-Ⅲ含量,起到抗凝和抑制血小板聚集作用,其对增强纤溶系统活性也有肯定作用。     

Improving natural principles with genetic engineering: TNK-tissue plasminogen activator.

The fibrinolytic system plays an important role in the physiological maintenance of blood flow and the dissolution of thrombi. Administration of fibrinolytic agents in indications such as myocardial infarction, pulmonary embolism, deep vein thrombosis or stroke, therefore, offers a rational means to dissolve pathological thrombi and restore vascular patency. The functional domains of the physiological tissue plasminogen activator (t-PA) provide fibrin specificity and serine protease activity for plasminogen cleavage and binding to liver receptors which gives the molecule a short half-life. In order to combat acute thromboembolic events such as myocardial infarction, the structure of the natural t-PA molecule was genetically modified to prolong its half-life, to increase its fibrin-specificity and to improve its resistance to plasminogen activator inhibitor. These features of TNK-t-PA allow bolus administration in emergency situations, early reperfusion of the blood vessel and a low rate of bleeding complications, thus improving the overall benefit to patients.     

犬脑栓塞血浆u-PA和u-PAR变化的实验研究

目的 观察犬脑栓塞前后血浆尿激酶型纤溶酶原激活剂(urokinase-type plasminogen activator,u-PA)和尿激酶型纤溶酶原激活剂受体(urokinase-type plasminogen activator receptor,u-PAR)的变化.方法 自体动脉血凝固制备栓子,使用介入方法建立犬脑栓塞模型.观察栓塞前和栓塞后2h、3h血浆u-PA和u-PAR的变化.结果 栓塞前和栓塞后2h、3h血浆u-PA和u-PAR水平差异无统计学意义,ρ＞0.05.结论 犬脑栓塞前和栓塞后3小时内血浆u-PA和u-PAR变化不明显.     

Renoprotective effects of fenofibrate in diabetic rats are achieved by suppressing kidney plasminogen activator inhibitor-1

To investigate mechanisms of protective effects of fenofibrate on the diabetic kidney, male Wistar rats were divided into control, untreated diabetes, and fenofibrate-treated (32 mg kg(-1) d(-1), 8 weeks) diabetes groups. Diabetes induced by streptozotocin (25 mg/kg) and a high-fat diet was characterized by the disorders of plasma glucose and lipids. In untreated diabetic rats, there were increases in glomerular volume, matrix content, expressions of laminin and urinary albumin excretion. These nephropathies were associated with the upregulations of plasminogen activator inhibitor 1 (PAI-1) mRNA expression and its protein activity in the renal cortex, and a significant increase in transforming growth factor beta1 (TGF-beta1) expression. Treatment with fenofibrate suppressed the expression of PAI-I mRNA and its protein activity, and inhibited TGF-beta1 overexpression. It also partially reversed metabolic disorders and pathophysiologic changes associated with diabetic nephropathy. Our results indicate that fenofibrate delays the progression of diabetic nephropathy in rats to some extent. These renoprotective effects are likely to be achieved through suppression of PAI-1 and TGF-beta1 in the renal cortex, and consequently less extracellular matrix deposition.     

蚓激酶胶囊治疗脑梗死患者的疗效和安全性

目的:评价蚓激酶胶囊治疗脑梗死的疗效和安全性.方法:采用多中心、随机双盲、安慰剂对照(2∶1)临床试验设计,73例发病3周后用药的脑梗死患者,分治疗组(n=50)和对照组(n=23),分别口服蚓激酶肠溶胶囊60万U和安慰剂2粒,tid,给药28d.统一实验室检测病例的凝血、纤溶、血液流变学指标,并评价患者的神经功能缺损和生活能力缺损程度.结果:治疗28d后,治疗组凝血酶原时间(PT)和部分凝血活酶时间(APTT)延长;纤维蛋白原(Fg)降低,D-二聚体含量增加;组织型纤溶酶原激活物(t-PA)含量提高,纤溶酶原激活物抑制物(PAI)含量降低;血浆黏度和全血黏度改善,且均具有显著性.安慰剂对照组则改变不明显.临床神经功能缺损评价,2组均有改善,但是治疗组恢复明显,治疗组有效率为88%,对照组47.8%.73例患者中,治疗组出现1例轻度上消化道出血(2%),无肝肾功能影响.结论:百奥蚓激酶胶囊治疗脑梗死安全有效,可作为治疗和预防缺血性脑血管病的有效药物.     

Plasminogen activation-based thrombolysis for ischaemic stroke: the diversity of targets may demand new approaches

The plasminogen activating enzyme system has been exploited and harnessed for therapeutic, mainly thrombolytic benefit for many years. While plasminogen activator-based thrombolysis turned out to be a resounding success, it has become apparent that the "plasminogen activating system" per se is not only designed to simply remove fibrin and some other matrix proteins. Indeed, the plasminogen activators and the plasminogen activator inhibitors have important effects on cell signalling through both proteolytic and non-proteolytic means and can promote unwanted side effects, particularly in the brain. Tissue type plasminogen activator (t-PA) was heralded as a fibrin-selective plasminogen activator and subjected to clinical development in the early 1980's initially for the treatment of patients with myocardial infarction. t-PA was given FDA approval in the mid 1990's for use in ischaemic stroke patients, but it could only be administered within a short 3h window post- stroke as later use was associated with an increased risk of intracerebral haemorrhage. Hence only a small percentage of these patients were eligible for thrombolysis to restore blood flow to the brain. Since t-PA-mediated plasmin generation is not only impacting on the cerebral blood clot, extending the therapeutic time window for thrombolysis is not a simple task. The ultimate success will depend on how well the future generation of thrombolytic agents promote efficacious removal of a fibrin clot without promoting collateral damage particularly in the brain.     

阿替普酶溶栓后发生颅内出血的相关因素研究

目的：采用大鼠脑梗死模型,考察静脉注射阿替普酶（rt-PA）溶栓后基质金属蛋白酶9（MMP-9）、组织纤溶酶原激活物与纤溶酶原激活物抑制因子的比值（t-PA/PAI-1）,血管性血友病因子（VWF）、凝血八因子（FⅧ）、凝血七因子（FⅦ）与颅内出血不良反应的相关性。方法：大鼠被随机分为3组：阿替普酶组、对照组、假手术组,阿替普酶组为成功构建大脑中动脉血栓栓塞模型后静脉注射阿替普酶;对照组为成功构建大脑中动脉血栓栓塞模型;假手术组为仅进行颈动脉暴露不进行血栓栓塞操作,手术后对大鼠进行神经功能评价。阿替普酶组分别在造模前、造模后2 h、给药后4 h采血,其他两组采血时间与阿替普酶组对应。比较三组间血浆内MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ的含量。采血后对大鼠进行灌注取脑,脑组织切片进行TTC染色,在白色脑梗死区域内有红色出血点及血肿认定为出血。阿替普酶组大鼠根据是否发生颅内出血,分为出血组与未出血组,并进一步比较两组间MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ的变化差异及其与颅内出血的相关性。结果：阿替普酶组、对照组、假手术组各28只,其中阿替普酶组出血8只;对照组出血2只;假手术组出血0只。血浆中的MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ在3组内3个时间点均无显著性差异（P>0.05）,且组间比较均无显著性差异（P>0.05）;进一步比较阿替普酶组出血动物与未出血动物血浆中的MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ,未发现统计学差异（P>0.05）。结论：使用阿替普酶溶栓后,通过检测血浆中的MMP-9、t-PA/PAI-1、VWF、FⅦ、FⅧ,难以预测溶栓后出血不良反应的发生。     

Mechanisms of activation of tissue-type plasminogen activator

Tissue-type plasminogen activator (t-PA) is an important component of the fibrinolytic system. t-PA is released into the circulation as a one-chain peptide with little enzyme activity. There exist several mechanisms which enhance plasminogen activation rate by t-PA: 1. activation of enzyme activity of one-chain t-PA by fibrin binding; 2. activation of enzyme activity by transforming one-chain to two-chain t-PA by plasmin; 3. stimulation of plasminogen activation by forming a ternary complex of t-PA, plasminogen and fibrin; 4. stimulation of plasminogen activation by forming Lys-plasminogen, which has a higher affinity to fibrin and is a better substrate for t-PA than Glu-plasminogen; 5. enhancement of ternary complex concentration after initiation of fibrinolysis due to tighter binding of t-PA and plasminogen to partially degraded fibrin.     

卡托普利和氯沙坦对自发性高血压大鼠纤溶功能的影响

目的:观察卡托普利和氯沙坦对自发性高血压大鼠(SHR)纤溶酶原激活物抑制剂-1(PAI-1)和组织型纤溶酶原激活物(t-PA)血浆活性及组织表达的影响。方法:SHR分为卡托普利组、氯沙坦组和对照组,用发色底物法测血浆PAI-1和t-PA活性,RT-PCR半定量法测组织表达。结果:SHR主动脉组织PAI-1表达增加,卡托普利(P<0.01)和氯沙坦(P<0.05)使PAI-1表达显著降低。结论:转换酶抑制剂卡托普利和血管紧张素II受体1拮抗剂氯沙坦可减少早期SHR主动脉PAI-1表达,改善局部的纤溶平衡和血管重构。