胺碘酮、美托洛尔对家免急性心肌梗死血小板活化、纤溶活性、内皮血管活性物质的影响

目的：探讨胺碘酮、美托洛尔对兔急性心肌梗死(AMI)血小板活化、纤溶活性、内皮血管活性物质的影响。方法：新西兰家兔50只，随机分为5组，每组10只。I组：假手术组，Ⅱ组：AMI组，Ⅲ组：AMI 利多卡因组，Ⅳ组：AMT 胺碘酮组，Ⅴ组：AMI 美托洛尔组；Ⅱ、Ⅲ、Ⅳ、Ⅴ组分别结扎冠状动脉左室支中点后，4h取血分别测定血栓素B2(TXB2)、6—酮—前列腺素F1a(6—Keto—PGF1a)、内皮素(ET)、一氧化氮(NO)和组织型纤溶酶原激活剂(t—PA)、纤溶酶原微活剂抑制物(PAI)水平；摘取心脏，测定心肌梗死范围。结果：Ⅱ、Ⅲ、Ⅳ、Ⅴ组血浆TXB2、ET、NO浓度和则活性显著高于I组(P＜0．01)，6—Keto—PGF1a浓度和t—PA活性显著低于I组(P＜0．01)，Ⅱ、Ⅲ、Ⅳ组之间比较，血浆TXB2、6—Keto—PGF1a。浓度、t—PA活性及心肌梗塞范围无显著差异(P＞0．05)，Ⅳ组血浆ET、NO浓度和PAI水平明显低于Ⅱ组（P＜0．01)，Ⅴ组血浆TXB2、ET、NO浓度和PAI水平明显低于Ⅱ组(P＜0．01)，6—Keto—PGF1Aa。浓度、t—PA活性显著高于Ⅱ组(P＜0．01)，心肌梗塞范围小于Ⅱ组(P＜0．01)。结论：胺碘抑制AMI早期PAI活性，减少ET和NO的释放；美托洛尔抑制AMI早期血小板活化，改善纤溶活性，减少ET和NO的再释放，缩小心肌梗塞范围。利多卡因无上述作用。     

蚓激酶（普恩复）治疗脑梗塞时抗凝和纤溶变化的临床研究

目的：探讨蚓激酶（普恩复）治疗急性脑梗塞时抗凝和纤溶的变化。方法：随机选择31例脑梗塞例患者，服药前后对患者行神经功能缺失评分、血浆中KPTT、PT、FIB、t－PA、PAI、D－二聚体的测定，并与以丹参治疗的20例脑梗塞患者进行对照。结果：患者口服蚓激酶后（400mg，3次／日），KPTT明显延长（P＜0．05），FIB明显减少（P＜0．05），t－PA活性明显增强（P＜0．01），D－二聚体明显增加（P＜0．01），以上指标在对照组中治疗前后无明显变化（P＞0．05）。治疗组、对照组PT、PAI在用药前后均无明显变化（P＞0．05）。结论：蚓激酶治疗脑梗塞取得疗效与内凝血途径抑制、纤溶的激活有关。     

金纳多改善冠心病高粘状态的临床观察

将冠心病伴血液高粘状态60例随机分为（1）对照组：用常规药物治疗；（2）金纳多组：在常规治疗基础上加用金纳多。对照组总有效率73．3％。金纳多组总有效率是90．1％（P＜0．01）。发现金纳多组红细胞压积明显降低（P＜0．01），血浆粘度及血小板聚集率降低，血浆纤溶酶原激活剂抑制物（PAI）活性降低，血浆组织型纤溶酶原激活剂（t－PA）活性升高。在高放大倍数布氏显微镜视野下，用药后血小板呈解聚集状态。结果揭示：金纳多能明显改善冠心病时的高粘状态，尤其在抑制血小板聚集方面作用明显，并且无副作用，是临床有前途的防治冠心病药物。     

蚓激酶对中风后遗患凝血—纤溶功能影响的前瞻性，随机、双盲对照研究

目的：探讨蚓激酶（普恩复）对凝血纤溶系统的作用。方法：采用前瞻性、随机、双盲对照研究的方法,对52例缺血性中风慢性期患者服药前后行神经功能缺失评分,血浆中KPTT、PT、FIB,t-PA,PAI-1,D-dimer,vWF、血小板聚集率进行测定。结果：患者口服6个月后（400mg,3次／日）神经功能缺失评分减少（P＜0．05）,FIB减少（P＜0．05）,t－PA活性明显增强（P＜0．01）,vWF含量明显降低（P＜0．01）,以上指标在安慰剂组无明显变化（P＞0．05）。 治疗组、安慰剂组KPTT、PT、PAI－1在用药前后均无明显变化（P＞0．05）。6个月时血小板聚集率抑制最大,聚集率的抑制与vWF的降低呈显著正相关（P＜0．05）与t－PA活性的增强呈显著负相关（P＜0．05）。结论：蚓激酶对缺血性中风慢性期患者所起的作用与纤溶激活,血小板聚集的抑制有关。     

纤溶酶原激活物抑制剂-1与肥胖

纤 溶系统由纤溶酶原、纤溶酶原激活物 ( plasminogenac tivatorPA)和激活物特异性抑制剂 (plasminogenacti vatorinhibitorPAI)、纤溶酶及纤溶酶抑制物组成 ,其主要功能是通过纤溶酶溶解纤维蛋白而将其从循环系统中清除出去。PAI是纤溶系统活性主要的生理调节物 ,它在体内有多种形式 ,包括内皮细胞型 (PAI 1)、胎盘型 (PAI 2 )、尿型 (PAI 3)和连接蛋白酶 1(proteasenexin 1) ,其中PAI 1在纤溶活性调节中起着重要作用 ,它主要灭活组织型纤溶酶原激活物 (t PA)。PAI 1和t PA之间的平衡对维持纤溶系统正常功能十分重要。临床和流…     

β-受体阻滞剂对家兔心肌缺血再灌注后纤溶活性及血管活性物质含量的影响

探讨艾司洛尔、索他洛尔、美托洛尔和卡维地洛对家兔心肌缺血再灌注后纤溶活性、血管内皮活性物质含量的影响。新西兰大白兔 5 8只 ,随机分为 6组 ,Ⅰ组 :AMI组 ,Ⅱ组 :缺血 再灌注 (ischemicreperfusion ,IR)组 ,Ⅲ组 :IR +艾司洛尔组 ,Ⅳ组 :IR +索他洛尔组 ,Ⅴ组 :IR +美托洛尔组 ,Ⅵ组 :IR +卡维地洛组 ;制作IR动物模型 (除AMI组 ) ,缺血 6 0min后再灌注 2 4 0min ,分别于缺血前、再灌注前 ,再灌注 2 4 0min后取血测定t PA、PAI 1的活性和ET、NO浓度。结果显示 :冠脉结扎后 ,血浆ET、NO浓度和PAI 1活性显著高于结扎前 ,而t PA活性显著低于结扎前 (P <0 0 1) ,再灌注后 ,血浆ET、NO浓度和PAI 1活性进一步升高 ,t PA活性进一步下降 (P <0 0 1)。与IR组对比 ,各组NO的浓度再灌注后无显著性差异 ,艾司洛尔组再灌注后血ET浓度显著降低 (P <0 0 1) ,血t PA、PAI 1活性无明显的变化 ;索他洛尔、美托洛尔、卡维地洛均能显著的升高再灌注后t PA活性 ,降低血PAI 1活性和ET浓度 (P <0 0 1)。提示 :索他洛尔、美托洛尔、卡维地洛有改善缺血再灌注过程中纤溶活性、抑制内皮细胞释放ET的有益作用 ;艾司洛尔能抑制缺血再灌注过程中ET的释放 ,对纤溶活性无明显的影响     

丹参对家兔急性缺血及再灌注心肌易损期和不应期的影响

本文采用程序性电刺激测定家兔心室易损期（VVP）和有效不应期（ERP）,观察了丹参对缺血和再灌注心肌的保护作用。结果表明,急性心肌缺血（AMI）和再灌注时,丹参组动物VVP明显低于对照组（分别P＜0．05及0．01）,ERP有所延长,但仅在再灌时明显大于对照组（P＜0．05）;AMI时的室颤（VF）发生率明显低于对照组（P＜0．01）,上述结果提示丹参可减轻缺血及再灌注损伤所致的心肌电生理改变,从而降低心肌的易损性。     

糖尿病大鼠血管糖基化终产物含量与其受体的ICAM—1表达的关系

探讨糖尿病大鼠血管组织糖基化终产物（AGEs)含量与其受体（RAGE）和细胞间粘附因子－1（ICAM－1）表达的关系。复制糖尿病大鼠模型,采用荧光法、RT－PCR及原位杂交方法检测主动脉及心肌组织的AGEs含量以及RAGE和ICAM－1基因的表达。发现糖尿病大鼠主动脉和心肌组织AGEs含量升高（P＜0．01）;RAGE和ICAM－1基因表达增强（P＜0．05－0．05）;AGEs含量与RAGE及ICAM－1呈明显正相关（P＜0．01）;氨基胍治疗可缓解上述指标的变化。提示 AGEs可诱导RAGE和ICAM－1的表达。推测AGEs-RAGE相互作用是引起糖尿病血管内皮细胞功能紊乱和损伤的关键环节。     

肝素对大鼠Thy-1肾炎u-PA/PAI-1表达的影响

目的：研究尿激酶型纤溶酶原激活物／Ⅰ型纤溶酶原激活物抑制因子（u-PA/PAI-1)在大鼠Thy-1肾炎病变进展过程中的变化，以及肝素对其表达的影响。方法：以抗Thy-1单抗成功制备大鼠Thy-1肾炎模型，并用肝素对其进行治疗，分别于1、3、7、14、21、28d处死动物并分别取其肾皮质。应用RT－PCR及Western blot方法检测肾皮质u-PA/PAI-1 mRNA及蛋白表达的变化，以观察肝素对其表达的影响。结果：RT－PCR法显示肾炎模型组（G组）于3－28d的肾皮质u-PA mRNA和3－21d的肾皮质PAI－1 mRNA的表达均高于对照组（P＜0.05或P＜0.01)；肝素治疗组（H组）仅21d时肾皮质u-PA mRNA的表达高于G组（P＜0.05)，而PAI-1 mRNA的表达于3－28d时均低于G组（P＜0.05)。Western blot结果显示3－28d时，G组u-PA和PAI－1蛋白表达量高于对照组（P＜0.05或P＜0.01)，这与RT－PCR检测结果相似；H组肾皮质u-PA蛋白表达量与G组相比差异无显著性，而3－21d时PAI－1蛋白表达量均低于G组（P＜0.05或P＜0.01)。结论：大鼠Thy-1肾炎肾皮质u-PA与PAI－1的表达均随肾小球病变的进展而增强，肝素治疗可能通过干扰或抑制u-PA和PAI－1的表达而发挥其治疗作用。     

锡类散凝胶对兔输液性静脉炎治疗效果的初步观察

目的探讨锡类散凝胶对兔实验性输液性静脉炎的治疗效果及可能机制。方法将大白兔随机分为对照组、静脉炎组和锡类散治疗组，每组20只。静脉炎组在耳缘静脉注射甘露醇构建实验眭输液性静脉炎动物模型，对照组以生理盐水替代甘露醇，治疗组在造模前经锡类散预处理；在造模后相应的时间点检测兔血浆中TT（凝血酶时间）、PT（凝血酶原时间）、APTT（活化部分凝血酶时间）、PAI-1（I型纤溶酶原激活物抑制因子）和t—PA（组织型纤溶酶原激活剂）含量，并作病理学检查及评分，最后进行统计分析。结果治疗组与静脉炎组相比较（P〈0．05），能明显纠正因甘露醇而造成的高凝状态，有效降低血清t—PA水平及减轻输液静脉损害；而PAI—1含量在三组之间没有统计学差异（P〉0．05）。结论锡类散凝胶能有效改善甘露醇所致的输液胜静脉炎损害，其机制可能通过抑制血清t—PA升高而发挥治疗作用。     

卡托普利对家兔急性心肌梗塞早期血小板活化及纤溶活性的影响

本研究观察了家兔急性心肌梗塞（ＡＭＩ）早期血浆血小板α－颗粒膜蛋白（ＧＭＰ－１４０）、血栓素Ｂ２（ＴＸＢ２）、组织型纤溶酶酶原激活剂（Ｔ－ＰＡ）及其抑制物（ＰＡＩ－１）水平的变化及卡托利干预的ＰＡ活性显著降低；相关分析表明，血浆ＧＭＰ－１４０浓度与ＰＡＩ－１活性显著正相关。卡托普利干预后，血浆ＧＭＰ－１４０浓度、ＴＹＸＢ２浓度、Ｔ－ＰＡ浓度、ｔ－ＰＡ含量、ＰＡＩ－１活性均明显降低，而ｔ－ＰＡ活性显     

Induction of t-PA Synthesis with intravenous bolus injection of vitamin A palmitate in vitamin a deficient rats

Retinoic acid and vitamin A palmitate induce tissue-type plasminogen activator (t-PA) synthesis in cultured human umbilical vein endothelial cells (HUVEC) in vitro without alteration of plasminogen activator inhibitor-] (PAI-1) synthesis. Therefore the effect of intravenous bolus injection of water-miscible vitamin A palmitate on the blood fibrinolytic system was investigated in normal and vitamin A deficient rats. In 5 normal rats, injection of 200000 IU/kg of vitamin A palmitate did not induce a significant increase in euglobulin fibrinolytic activity, t-PA antigen and PAI activity in plasma nor of t-PA and PAI-1 mRNA in the heart within 240 min after injection. In groups of 3–6 vitamin A deficient rats, injection of 200000IU/kg of vitamin A palmitate induced a significant increase in t-PA antigen in plasma (1.9-fold after 60 min and 2.9-fold after 120 min), but no significant increase in plasma euglobulin fibrinolytic activity. A 2-fold increase in PAI activity was observed 90 min after injection of both vitamin A palmitate as well as of its solvent, suggesting that this induction was non-specific. The increase in t-PA antigen coincided with a significant increase in t-PA mRNA in heart tissue: 2.3-fold after 60 min and 4.3-fold after 120 min. PAI-1 mRNA in heart tissue increased 3.6-fold 90 min after injection with vitamin A palmitate but, surprisingly, not after injection of solvent.It is concluded that intravenous bolus injection of vitamin A palmitate induces a specific increase of t-PA mRNA in the heart and of t-PA antigen secretion in plasma of vitamin A deficient rats.     

Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 levels in acute myocardial infarction

The cause of the circadian variation in the incidence of acute myocardial infarction (AMI) has not been identified. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) have opposing effects on thrombi. Hence, the extent of the clot, the size of the infarct and outcome of patients could depend on t-PA and PAI-1 levels. In an effort to elucidate the pathophysiologic basis of circadian variation of AMI, we investigated the presence of a possible corresponding circadian variation in the levels of endogenous t-PA and PAI-1 in patients diagnosed to have AMI and the effects of hypertension, diabetes and site of the infarct on these levels. We estimated the levels of t-PA and PAI-1 in platelet-poor plasma of 42 patients with AMI on admission, using the enzyme-linked immunosorbant assay. Although not statistically significant, patients having an AMI in the morning hours had the highest t-PA:PAI-1 ratio. The normal circadian variation in PAI-1 levels was lost in patients with AMI, probably due to the disease process. Also, the t-PA levels in hypertensive patients were significantly lower than in nonhypertensives. PAI-1 levels were also significantly lower in patients with anteroseptal than in inferior and anterolateral AMI. This relationship between the fibrinolytic potential and the site of infarction needs further study. Furthermore, t-PA levels on admission were significantly lower in survivors and may have a predictive value in determining the outcome.     

Chronic glucocorticosteroid administration modulates the response of the fibrinolytic system to bacterial lipopolysaccharide

An in vivo rat model was used to study the effect of chronic glucocorticosteroid administration on the response of the fibrinolytic system to lipopolysaccharide (LPS). Male Lewis rats were injected subcutaneously for 30 consecutive days with either saline or saline containing 0.1 μg/g dexamethasone. On the thirty-first day, the rats were challenged with intraperitoneal injections of LPS (0.5 μg/g). Plasma and selected tissues (liver, kidney, heart, lung, muscle, and fat) were removed for analysis at various times after LPS injection. LPS treatment caused a rapid rise in plasma type 1 plasminogen activator inhibitor (PAW) activity in both groups. However, in the dexamethasone-pretreated animals a transient decline in PAI-1 activity was detected at 4 h, coinciding with a transient increase in plasma tissue plasminogen activator (t-PA) activity and a marked elevation of t-PA messenger RNA (mRNA) levels in the lung. Plasma t-PA activity returned below basal levels by 8 h and did not differ between the two groups at later times. At 24h, PAI-1 activity remained significantly elevated in the dexamethasone-pretreated rats while declining in the saline-pretreated rats. A greater induction of PAI-1 mRNA was evident in the dexamethasone-pretreated rats in all six tissues examined. Notably, a 3-fold greater increase in PAI-1 mRNA was detected in the liver at 24h, corresponding with the sustained elevation in plasma PAI-1 activity at this time. Collectively, these data suggest that chronic glucocorticosteroid treatment potentiates the induction of both t-PA and PAI-1 gene expression by LPS, resulting in an initial transient increase in plasma t-PA activity followed by a more sustained elevation in plasma PAI-1 activity.     

Effect of acute alcohol ingestion on the fibrinolytic activity

Effects of alcohol consumption on the function of fibrinolytic system were studied. The group which consisted of 12 male volunteers consumed standardised amounts of whisky. 3 blood samples for the assessment of euglobulin clot lysis time, t-PA, urokinase, PAI-1 and its complex with t-PA were taken: 1 before, 1 taken 45 min after and 1 on the next morning after drinking. No change was noted in those parameters 45 min after the consumption of ethanol. Alcohol ingestion had a specific tendency to decrease fibrinolytic activity on the next day after drinking. Therefore, acetaldehyde, the main metabolite of ethanol, rather than ethanol itself may be responsible for the enhancement of PAI-1 secretion by endothelial cells. These results show that the fibrinolytic system does not account for commonly accepted protection from coronary heart disease mediated by moderate consumption of alcohol.     

黄腐酸钠对糖尿病大鼠视网膜病变的作用

目的 :探讨黄腐酸钠对糖尿病大鼠视网膜病变 (DR)的治疗作用及其机制。方法 :对佐菌素诱导的糖尿病大鼠早期给予 0 .5 %黄腐酸钠 3 0mg/kg皮下注射 ,1次 /日 ,共 6个月。利用光镜和透射电镜观察其视网膜组织的形态改变 ,同时检测血浆纤溶酶原激活剂 (t PA)、纤溶酶原激活剂抑制物 (PAI 1)活性及循环血中粒细胞表面抗原CD11a、CD11b。结果 :(1)黄腐酸钠治疗组视网膜组织光镜下及超微结构变化较病变组大鼠有明显改善 ,毛细血管基底膜的增厚明显减轻 (P <0 .0 1)。 (2 )治疗组t PA、PAI 1活性的改变较病变组得以纠正 (P <0 .0 1)而接近于正常对照组水平 (P <0 .0 5 )。基底膜厚度与血浆t PA活性呈显著负相关。 (3 )治疗组CD11a、CD11b的表达受到抑制 (P <0 .0 5 )。结论 :黄腐酸钠对DR的进展有一定的抑制作用。此作用可能与维持血浆t PA、PAI 1平衡而改善纤溶活性 ,减少白细胞粘附有关。     

代谢综合征患者纤溶活性与胰岛素抵抗的关系

目的:探讨代谢综合征患者血浆纤溶活性及与胰岛素抵抗的关系。方法:选择单纯代谢综合征患者36例,代谢综合征合并冠心病患者44例和健康人群对照20例。观察一般情况,并测定血浆纤溶酶原激活抑制物-1(PAI-1)和组织型纤溶酶原激活物(t-PA)、纤维蛋白原(Fib)、空腹血糖(FBG)、空腹血胰岛素(Ins)和血脂等指标;计算胰岛素敏感指数(ISI)。结果:代谢综合征患者的ISI较正常对照组明显下降(P<0.05);血浆PAI-1、Fib等明显升高(P<0.05)。代谢综合征合并冠心病组PAI-1与Fib、Ins正相关,与ISI、高密度脂蛋白(HDL)负相关。结论:代谢综合征患者存在明显的胰岛素抵抗和纤溶活性异常,同时纤溶活性异常与胰岛素抵抗相关。     

Familial thrombophila associated with high levels of plasminogen activator inhibitor

A family with defective fibrinolytic abnormalities and recurrent thrombotic events is described. Impaired fibrinolysis was associated with high activity and concentration of fast-acting plasminogen activators inhibitor (PAI-1). Acquired conditions associated with PAI-1 increase were excluded. After venous occlusion testing, a different behaviour of fibrinolytic activity inhibition was seen in the family members. In the propositus and in two relatives only tissue (t-PA) plasminogen activity inhibition was found; in two other members, both t-PA and urokinase-type plasminogen activities were completely inhibited by the high PAI-1 levels. This fibrinolytic defect seems to be familial and transmitted as an autosomal trait.