心肌梗死患者血清血管紧张素转换酶与血浆纤溶酶原激活剂抑制物1的活性及其相关性

目的：测定心肌梗死患者及正常人血清血管紧张素转换酶、血浆纤溶酶原激活剂抑制物1水平，并通过其相关性分析探讨肾素-血管紧张素系统与纤溶之间的关系。 方法：选择中山大学附属第二医院2002-12／2003-10收治的心肌梗死患者95例，以同期健康体检者87例为对照组。应用比色法测定两组受试者血清血管紧张素转换酶活性，同时应用发色底物法测定血浆纤溶酶原激活剂抑制物1水平，并对其结果进行直线相关性分析。 结果：心肌梗死组93例、对照组87例进入结果分析。①心肌梗死组血清血管紧张素转换酶活性和血浆纤溶酶原激活剂抑制物1水平均高于对照组[（3．60&;#177;0．97），（2．84&;#177;0．82）μkat／L；（0．85&;#177;0．19），（0．66&;#177;0．20）AU／mL。P均〈0．01]。②心肌梗死组与对照组血清血管紧张素转换酶、血浆纤溶酶原激活剂抑制物1水平均呈显著正相关（r=7108，0．7829，P均〈0．01）。 结论：①血清血管紧张素转换酶、血浆纤溶酶原激活剂抑制物1活性的增高与心肌梗死明显相关。②肾素-血管紧张素与纤溶之间存在一定的联系，血管紧张素转换酶可能通过影响血浆纤溶酶原激活剂抑制物1活性而参与对纤溶平衡的调节，两者之间的关系对冠状动脉粥样硬化性心脏病的发病起到重要作用。     

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。     

冠状动脉粥样硬化性心脏病危险因素与血管紧张素转换酶基因多态性及纤溶酶原激活物抑制物1活性的相关性

目的:观察传统冠状动脉粥样硬化性心脏病危险因素与血管紧张素转换酶基因插入/缺失多态性及血浆纤溶酶原激活物抑制物1活性的关系。方法:纳入2004-12/2005-06中山大学附属第二医院常规体检者297例,排除有明确冠状动脉粥样硬化性心脏病不稳定型心绞痛、急性心肌梗死病史者;既往曾行冠状动脉介入治疗者;心电图有明确心肌缺血或运动试验阳性者;有明确肝、肾功能障碍、肿瘤等器质性疾病者。应用PCR方法扩增血管紧张素转换酶基因特异性片段,同时应用发色底物法测定纤溶酶原激活物抑制物1活性。设计调查表调查冠状动脉粥样硬化性心脏病危险因素,按下述标准定义:①原发性高血压按《2004年中国高血压防治指南》的标准定义和诊断。②糖尿病诊断符合国际糖尿病联盟2005全球2型糖尿病诊治指南诊断标准。③血脂异常定义为:空腹血清总胆固醇≥6.0mmol/L或/和低密度脂蛋白胆固醇≥4.16mmol/L;或/和高密度脂蛋白胆固醇≤1.04mmol/L;或/和三酰甘油≥2.2mmol/L。④吸烟指目前吸烟每天大于10支和既往吸烟戒断不足2年者。⑤肥胖指体质量指数≥24kg/m2者。观察整体人群血管紧张素转换酶各基因型之间、冠状动脉粥样硬化性心脏病危险因素与纤溶酶原激活物抑制物1活性的关系。结果:纳入血样297例,全部进入结果分析。①在整体人群中血管紧张素转换酶各基因型之间纤溶酶原激活物抑制物1水平相似,差异无统计学意义(P>0.05)。②多重线性回归分析显示三酰甘油、总胆固醇、空腹血糖、收缩压、舒张压,与纤溶酶原激活物抑制物1活性呈显著正相关(P均<0.01)。③在无冠状动脉粥样硬化性心脏病危险因素的男性体检者,DD基因型血浆纤溶酶原激活物抑制物1活性显著高于ID基因型与II基因型[(40.3±3.2),(33.9±2.1),(32.6±4.9)AU/mL,P<0.01]。在无危险因素的女性体检者,DD基因型血浆纤溶酶原激活物抑制物1活性虽高于ID基因型与II基因型,但差异无统计学意义[(36.2±1.3),(34.1±4.4),(33.7±3.6)AU/mL,P>0.01]。结论:传统冠状动脉粥样硬化性心脏病危险因素与血浆纤溶酶原激活物抑制物1水平相关;在排除传统冠状动脉粥样硬化性心脏病危险因素后血管紧张素转换酶基因DD型与血浆纤溶酶原激活物抑制物1水平的增高相关,血管紧张素转换酶基因型在影响纤溶平衡中可能起重要作用。     

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。     

隐匿性冠心病病人血浆组织型纤溶酶原激活物及其抑制物活性…

用底物显色法测定了２９例隐匿性冠心病病人的组织型纤溶酶原激活物和纤溶酶原激活物抑制物的活性水平，结果发现隐匿性冠心病病人的ｔ－ＰＡ，ＰＡＩ活性与对照组比较，差异无明显性（Ｐ〉０．０５），提示血液中ｔ－ＰＡ，ＰＡＩ的活性异常仅是冠心病病人的发病因素之一。     

纤溶酶原激活物抑制物-1与动脉粥样硬化关系的研究

目的 通过对动脉粥样硬化（AS）兔血清和粥样硬化斑块中纤溶酶原激活物抑制物-1（PAI-1）表达的研究,探讨PAI-1在AS中的作用.方法 16只雄性大耳白兔随机分为正常饮食组和高脂饮食组,每组8只,饲养16周.两组白兔均于0周、16周取耳缘静脉血,检测血清中PAI-1 的水平;16周后处死,应用免疫组化方法检测PAI-1在主动脉粥样硬化斑块中的表达.结果 正常饮食组和高脂饮食组0周血清中PAI-1水平差异无显著性（P＞0.05）;高脂饮食组16周后血清PAI-1水平较0周显著增加（P＜0.01）;免疫组化结果显示高脂饮食组主动脉壁PAI-1 的表达明显高于对照组（P＜0.01）.结论 动脉粥样硬化的发生伴有血清和粥样斑块中PAI-1表达增加,PAI-1可能参与了AS的形成.     

替米沙坦对高血压患者胰岛素抵抗及血浆纤溶酶原激活物抑制物1的作用

高血压患者的胰岛素抵抗（IR）及纤溶受损促进其心脑血管并发症的发生和发展。研究显示血管紧张素Ⅱ（ATⅡ）受体拮抗剂具有良好抗高血压作用，替米沙坦（商品名：美卡素）作为一新型高选择性血管紧张素Ⅱ1型受体（AT1）拮抗剂，具有独特的激活过氧化物酶体增殖物激活受体γ（PPAR-γ）作用。PPAR-γ对糖和脂代谢具有重要作用，它的激活可促进碳水化合物代谢相关基因表达，改善糖尿病患者IR，并具有抗炎抗氧化及保护内皮功能作用。本研究观察了替米沙坦对高血压患者IR指数及血浆纤溶酶原激活抑制物1（PAI-1）的作用。     

脑梗死与纤溶酶原激活抑制物-1的相关性

目的:探讨纤溶酶原激活抑制物-1(plasainogenactivatorinhibitor-1,PAI-1)活性和PAI-14G/5G基因多态性与脑梗死的相关性。方法:用发色底物法和PCR及琼脂糖凝胶电泳技术检测了脑梗死患者52例(2001-06/2002-12上海第九人民医院神经内科收治)和31例正常对照者的血浆PAI-1活性和PAI-14G/5G基因多态性。结果:病例组和对照组PAI-14G/4G基因型所占比例分别为48%(25/52)和23%(7/31),差异有显著性意义(P<0.05);病例组和对照组血浆PAI-1活性分别为(10.77±0.80)和(10.05±0.86)kU/L,差异有非常显著性意义(t=3.8622,P<0.001);PAI-1活性与PAI-14G/5G基因型及血糖相关。结论:研究结果提示PAI-14G/4G基因型及PAI-1活性增高是脑梗死的危险因素。     

脑梗死患者胰岛素抵抗与血浆纤溶酶原激活物抑制物-1的关系

目的 明确脑梗死患者存在胰岛素抵抗(IR)，探讨IR与血浆纤溶酶原激活物抑制物-l(PAl-1)的关系。方法 选择62例脑梗死患者和35例健康体检者。测定空腹血糖(FBG)、空腹胰岛素(FINS)浓度和血浆PAl-l活性。计算胰岛素敏感指数(ISI)，并与神经功能缺失评分、梗死灶面积和PA1-l进行直线相关分析。结果 脑梗死患者FBG、FINS和PAI-l显著高于对照组：ISI显著低于对照组。脑梗死轻型组与脑梗死重型组之闻nNs、ISI和PAI-l存在显著差异。ISI与梗死灶面积、神经功能评分和PAI-l呈负相关；PAI-l与梗死灶面积和神经功能缺失评分呈正相关。结论 脑梗死患者存在胰岛素抵抗和纤溶活性的降低；IR和PAI-l与脑梗死患者病情轻重密切相关．IR和PAI-1活性增高可能导致脑梗死的形成和发展。     

Comparison of plasminogen activator inhibitor activity and antigen in plasma samples

A double antibody radioimmunoassay for determination of plasminogen activator inhibitor (PA-inhibitor) in plasma samples has been developed. The reliability of the method as assessed by determining the specificity, the accuracy, the detectability and the variability seems sufficient for use in clinical practice. The correlation between PA-inhibitor antigen as measured with this method and PA-inhibitor activity as measured with a spectrophotometric assay in 111 patients with thrombotic diseases was very good (r = 0.89). As calculated from the regression line or from the mean activity and mean antigen values a specific activity of about 800,000-900,000 arb U/mg was obtained for PA-inhibitor in these samples. In 15 healthy individuals a similar figure was obtained. The results suggest that PA-inhibitor in most plasma samples is fully active or close to fully active. PA-inhibitor activity and PA-inhibitor antigen have also been measured after venous occlusion. The data suggest that small amounts of PA-inhibitor is released on venous occlusion, but at the same time an inactivation takes place, most likely due to the formation of enzymatically inactive complex with simultaneously released t-PA.     

脑梗死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活性的变化与神经功能缺损的相关性

INTRODUCTIONItwasreportedthatlow-fibrinolysisstatecharacterizedwithdecreaseoftissue-typeplasminogenactivator(t-PA)activityandincreaseoftype1plasminogenactivatorinhibitor(PAI-1)activityexistedinthepathologicalprocessofarterioscleroticcerebralinfarction犤1犦.Butre-centanimalexperimentshowedthatmRNAoft-PAandu-PAex-pressedincreasinglyinischemiccerebraltissue犤2犦.Sofurtherobser-vationwasindispensable.Wetestedtheactivityofplasmat-PAandPAI-1of91patientswitharterioscleroticcerebralinfarct…     

ST段抬高型心肌梗死患者纤维蛋白原和D-二聚体的变化

目的 探讨ST段抬高型心肌梗死(STEMI)患者与冠状动脉造影阴性者纤维蛋白原和D-二聚体含量的差异.方法 选取我院2005年1月至2007年12月诊断为STEMI并行直接经皮冠状动脉介入(PCI)治疗的患者100例.同时选取冠状动脉造影阴性者100例为对照组.比较2组间纤维蛋白原和D-二聚体含量.结果 2组性别、年龄、高血压史、糖尿病史和吸烟史差异无统计学意义(P均0.05).STEMI组血浆纤维蛋白原含量为(2.38±0.91)g/L,对照组为(2.65±0.68)g/L,差异有统计学意义(t=-2.34,P<0.05).D-二聚体的平方根STEMI组为(13.23±5.08)μg/L,对照组为(9.40±5.03)μg/L,差异有统计学意义(t=5.36,P<0.01).血浆D-二聚体与纤维蛋白原含量比值的平方根STEMI组为(9.11±4.13),对照组为(5.92±3.35),差异有统计学意义(t=5.99,P<0.01).结论 STEMI患者的纤维蛋白原低于冠状动脉造影阴性的对照组,D-二聚体高于对照组,提示在STEMI急性期存在急性血栓形成和继发纤溶.     

Angiotensin converting enzyme DD genotype affects the changes of plasma plasminogen activator inhibitor-1 activity after primary percutaneous transluminal coronary angioplasty in acute myocardial infarction patients

Angiotensin converting enzyme (ACE) DD genotype, and plasminogen activator inhibitor (PAI-1) 4G/4G genotype have been reported to affect PAI-1 activity in control subjects and atherosclerotic patients, but no data are available on the influence of angiotensin II type 1 receptor (AT1R) A1166C polymorphism on the inhibitor levels. The degree of fibrinolytic activation after percutaneous transluminal coronary angioplasty (PTCA) has been found to affect the risk of restenosis. The aim of this study was to investigate the possible influence of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms on the changes of PAI-1 activity after primary successful percutaneous transluminal angioplasty. In 29 consecutive acute myocardial infarction patients, undergoing primary successful angioplasty, genotyping of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis, and PAI-1 plasma activity (chromogenic method) was assessed before and after angioplasty. Following angioplasty, PAI-1 activity increased in 10 of 29 patients and decreased or remained unchanged in 19 of 29. ACE DD genotype was significantly (P = 0.04) associated with an increase of PAI-1 activity post angioplasty (OR DD/ID+II = 6.5, CI 95% 4.83-8.22). Whereas no effect of PAI-1 4G/5G and AT1R A1166C polymorphisms on PAI-1 response to angioplasty was demonstrated, these data suggest that renin-angiotensin system genes are involved in the regulation of the fibrinolytic response to balloon injury, possibly affecting angiotensin converting enzyme activity. This interaction between the renin-angiotensin system and hemostasis may be a mechanism by which ACE DD genotype affects the risk of restenosis after percutaneous transluminal angioplasty.     

Standardization of methods for measuring plasminogen activator inhibitor activity in human plasma

We have standardized the measurement of plasminogen activator inhibitor type 1 (PAI-1) activity in plasma. One-chain tissue-type plasminogen activator (t-PA; EC 3.4.21.31; final activity, 5 int. units/mL) was incubated with plasma (final dilutions 1:4 to 1:40) in phosphate buffer (pH 7.4, ionic strength = 0.15) for 15 min at 37 degrees C, followed by acidification and measurement of residual t-PA activity by an amidolytic method. The PAI-1 activity assay was 98% specific for PAI-1 activity in samples from both pregnancy and nonpregnancy, and varied linearly with added plasma volume when the percent inhibition of t-PA was between 8% and 50%. For the standardized method, analytical recovery was 93 +/- 5%, the detection limit was 1.6 arbitrary units per milliliter (1 arb. unit of PAI-1 activity = inhibition of 1 int. unit of t-PA activity), and total imprecision was 10.2 (SD 0.7) arb. units/mL (CV = 7%, n = 20). The average PAI-1 activity in 10 healthy individuals drawn between 0800 and 1000 hours was 23.9 +/- 15.4 arb. units/mL. Compared with the standardized assay, two of three previously described assays underestimated PAI-1 activity in plasma by 77% and 85%, respectively.