氯沙坦和阿替洛尔对高血压患者纤溶系统及血浆血管性血友病因子的作用比较

目的 比较血管紧张素受体拮抗剂(ARB)氯沙坦和β受体阻滞剂阿替洛尔对原发性高血压患者纤溶系统及血浆血管性血友病因子(vWF)的影响.方法 轻中度原发性高血压患者60例随机分成氯沙坦组和阿替洛尔组(每组30例),分别给予氯沙坦50 mg/(次·d)或阿替洛尔50 mg/(次·d),共治疗8周.每4周随访1次,4周时血压如不达标(BP＜140/90 mm Hg)则加用双氢克尿噻12.5 mg/(次·d).治疗前后行血浆组织型纤溶酶原激活物(tPA)及纤溶酶原激活物抑制剂1(PAI-1)检测,并计算PAI-1/tPA作为纤溶参数,同时测定血浆vWF的含量.结果 两组的基线血压等一般情况具有可比性.治疗4周及8周时两组血压均较治疗前显著下降,组间比较无差异.同治疗前相比,氯沙坦组治疗8周时血浆PAI-1和vWF水平下降(P值分别＜0.05及＜0.01),PAI-1/tPA也有显著下降(P＜0.05),而tPA则无显著变化(P＞0.05);阿替洛尔组治疗8周时血浆PAI-1和vWF水平及PAI-1/tPA均无显著变化,而tPA则有所上升(P＜0.05).治疗后血浆vWF两组间比较,差异有非常显著意义.结论 氯沙坦治疗能改善原发性高血压患者的纤溶系统并降低血浆vWF,而阿替洛尔则未见有此作用.     

氯沙坦对高血压病人血压、凝血和纤溶活性的影响

目的观察高血压病人凝血和纤溶活性的改变,探讨血管紧张素Ⅱ受体拮抗剂氯沙坦对高血压病人血压以及凝血和纤溶系统的影响.方法将26例原发性高血压病人和30例正常对照组进行比较.所有入选对象1个月内未服任何降脂药物,停用降压药1周以上,禁食10h后,次晨抽取血样,测定各项指标.结果高血压病人胰岛素敏感性指数(ISI)和组织型纤溶酶原激活物(tPA)水平降低,而纤溶酶原激活物抑制剂-1(PAI-1)活性和血管性血友病因子(vWF)则升高.经多元逐步回归分析提示PAI-1与收缩压水平、总胆固醇和vWF呈显著正相关.高血压组给予氯沙坦50～100mg/d治疗,疗程6周,收缩压和舒张压明显下降;PAI-1活性较治疗前明显降低;而tPA活性较治疗前升高;ISI和vWF在治疗后无明显变化.结论高血压病人存在一定程度的胰岛素抵抗和凝血、纤溶功能紊乱.氯沙坦治疗能有效降低病人的血压,同时可以改善高血压病人的纤溶活性.     

氯沙坦对高血压病人血压、凝血和纤溶活性的影响

目的：观察高血压病人凝血和纤溶活性的改变。探讨血管紧张素Ⅱ受体拮抗剂氯沙坦对高血压病人血压以及凝血和纤溶系统的影响。方法：将26例原发性高血压病人和30例正常对照组进行比较。所有入选对象1个月内未服任何降脂药物。停用降压药1周以上，禁食10h后，次晨抽取血样，测定各项指标。结果：高血压病人胰岛素敏感性指数（ISI）和组织型纤溶酶原激活物（tPA)水平降低，而纤溶酶原激活物抑制剂-1（PAI-1）活性和血管性血友病因子（vWF)则升高，经多元逐步回归分析提示PAI-1与收缩压水平，总胆固醇和vWF呈显著正相关。高血压组给予氯沙坦50-100mg/d治疗，疗程6周，收缩压和舒张压明显下降；PAI-1活性较治疗前明显降低；而tPA活性较治疗前升高；ISI和vWF在治疗后无明显变化。结论：高血压病人存在一窍不通程度的胰岛素抵抗和凝血、纤溶功能紊乱，氯沙坦治疗能有效降低病人的血压，同时可以改善高血压病人的纤溶活性。     

氯沙坦对扩张型心肌病心力衰竭患者纤溶参数的影响

目的了解扩张型心肌病心力衰竭患者纤溶参数的变化,及氯沙坦对纤溶参数的影响.方法测定40名健康者和60例扩张型心肌痛心衰患者血浆纤溶酶原激活物(tPA)活性,纤溶酶原激活物抑制物-1(PAI-1)活性以及血管紧张素Ⅱ(AngⅡ)含量.将扩张型心肌病患者随机分成常规治疗组和氯沙坦组.治疗14天后复查tPA、PAI-1、AngⅡ. 结果与正常对照组相比,扩张型心肌病心衰患者tPA活性下降、PAI-1活性升高、AngⅡ含量上升(P＜0.01).治疗14天后,常规治疗组tPA与PAI-1的活性和AngⅡ含量无显著变化(P＞0.05);氯沙坦组tPA活性上升、PAI-1活性下降(P＜0.01),AngⅡ含量降低(P＜0.05).结论扩张型心肌痛心力衰竭患者纤溶参数明显异常,氯沙坦能改善纤溶参数活性.     

氯沙坦对原发性高血压患者纤溶功能的影响

目的观察氯沙坦对原发性高血压(EH)患者纤溶功能的影响。方法观察34例EH患者应用氯沙坦治疗4周后收缩压(SBP)、舒张压(DBP)、心率、血浆组织型纤溶酶原激活物(t-PA)、内皮细胞型纤溶酶原激活物抑制剂(PAI-1)水平的变化,并与30例健康人作比较。结果治疗前EH患者血浆t-PA水平明显低于对照组,而PAI-1水平明显高于对照组(均P<0.01)。氯沙坦治疗4周后,血压明显下降,心率无明显变化,血浆t-PA水平增加,但无统计学意义,而PAI-1水平明显降低,t-PA/PAI-1比值升高(均P<0.01)。结论EH患者存在着内源性纤溶功能紊乱,氯沙坦可以改善EH患者的纤溶功能。     

血管紧张素转换酶抑制剂对糖尿病大鼠血浆PAI-1和tPA活性的影响

目的 探讨血管紧张素转换酶抑制剂(ACEI)对糖尿病(DM)大鼠血浆纤溶酶原激活物抑制剂1(PAI-1)和组织型纤溶酶原激活物(tPA)活性的影响及其机制.方法 将链脲佐菌素诱导的DM大鼠分为正常对照组、培哚普利治疗组、培哚普利联合一氧化氮合酶(NOS)抑制剂治疗组.治疗4周后比较各组血浆PAI-1和tPA活性及PAI-1/tPA比值.结果 与正常对照组相比,DM大鼠血浆PAI-1活性和PAI-1/tPA比值显著升高,tPA活性降低.培哚普利治疗使PAI-1活性下降,tPA活性增加.联合NOS抑制剂在一定程度上抵消了培哚普利的这种作用.结论 DM状态下存在纤溶异常,ACEI能够通过内源性的NO改善纤溶平衡.     

疏血通注射液对心房颤动患者血栓前状态的影响

目的研究疏血通注射液对心房颤动患者血栓前状态的改善作用。方法将63例心房颤动患者随机分为疏血通组和对照组,疏血通组应用疏血通注射液治疗14d,对照组除不使用疏血通,其他用药与疏血通组相同。治疗前和治疗2周后测量两组血浆纤溶酶原激活物(tPA)及其抑制物(PAI-1)活性,D-二聚体(D-D)和血管性假血友病因子(vWF)水平。结果疏血通组和对照组在治疗前血浆tPA、PAI-1活性、D-D和vWF水平无统计学意义(P>0.05)。疏血通组治疗后血浆tPA活性显著性增高(P<0.05),血浆PAI-1活性、D-D和vWF水平均显著性下降(P<0.05),而对照组无显著性改变(P>0.05)。组间比较发现,疏血通组治疗后血浆PAI-1活性、D-D和vWF水平比对照组更低(P<0.05),而血浆tPA活性无显著增高(P>0.05)。结论短期疏血通静脉输注可以明显改善心房颤动患者的血栓前状态,这可能降低心房颤动患者的血栓栓塞危险。     

氯沙坦和尼群地平对高血压病患者E选择素、冯维布兰德因子等活性的影响

目的对比研究氟沙坦和尼群地平对原发性高血压(EH)患者血浆可溶性E选择素(sE-sel)、冯维布兰德因子(vWF)、纤溶酶原激活抑制物-1(PAI-1)活性的影响.方法60例EH患者随机分为二组,分别予以氯沙坦(50mg/d)和尼群地平(30mg/d)治疗4周,治疗前后抽血用酶联免疫方法(ELISA)测定血浆sE-sel、vWF、PAI-1活性.另选择30例健康人作对照组.结果氯沙坦组和尼群地平组患者治疗前sE-selectin、vWF、PAI-1活性较对照组均明显升高(P＜0.01);EH患者治疗后血压均明显下降(P＜0.01),氯沙坦组血浆sE-selectin(P＜0.01)、vWF(P＜0.01)、PAI-1(P＜0.05)活性较治疗前均有明显降低,而尼群地平组治疗后上述指标较治疗前均无明显降低(P＞0.05).结论EH患者存在高血浆水平sE-sel、vWF、PAI-1,表明存在血管内皮细胞功能障碍;与尼群地平比较,氯沙坦在降血压同时还可改善EH患者的内皮细胞功能障碍.     

氯沙坦对扩张型心肌病心力衰竭患者纤溶参数的影响

目的：了解扩张型心肌病心力衰竭患者纤溶参数的变化，及氯沙坦对纤溶参数的影响。方法：测定40名健康者和60例扩张型心肌病心衰患者血浆纤溶酶原激活物（tPA)活性，纤溶酶原激活物抑制物－1（PAI－1）活性以及血管紧张素Ⅱ（AngⅡ）含量，将扩张型心肌病患者随机分成常规治疗组和氯沙坦组。治疗14天后复查tPA、PAI-1、AngⅡ。结果：L与正常对照组相比，扩张型心肌病心衰患者tPA活性下降、PAI－1活性升高、AngⅡ含量上升（P＜0．01）。治疗14天后，常规治疗组tPA与PAI－1的活性和AngⅡ含量无显著变化（P＞0．05）；氯沙坦组tPA活性上升、PAI－1活性下降（P＜0．01），AngⅡ含量降低（P＜0．05）。结论：扩张型心肌病心力衰竭患者纤溶参数明显异常，氯沙坦能改善纤溶参数活性。     

脑血管球囊成形支架置入术治疗急性脑梗死的疗效及其对患者纤溶系统的影响

目的 探讨脑血管球囊成形支架置入术治疗急性脑梗死（AI）的临床疗效及其对患者纤溶系统的影响.方法 将68例AI患者随机分为两组各34例,观察1组给予尿激酶100万U静脉溶栓治疗,观察2组行脑血管球囊成形支架置入术治疗,术后口服氯吡格雷和阿司匹林.观察两组血流再通疗效,并检测其治疗前及治疗后1、7d的血管性假血友病因子（vWF）、组织型纤溶酶原激活物（tPA）、纤溶酶原激活物特异性抑制物（PAI-1）变化.另选体检健康者30例作为对照组.结果 观察2组血流再通率高于观察l组,P＜0.05.与对照组比较,观察组治疗前vWF、PAI-1、tPA升高,tPA/PAI-1降低,P均＜0.05;观察l、2组比较P＞0.05.治疗后ld观察组tPA、tPA/PAI-1升高,PAI-1降低,P＜0.05;治疗后7d,观察1组tPA、tPA/PAI-1降低,观察2组vWF升高,P均＜0.05.结论 脑血管球囊成形支架置入术治疗AI可使梗死相关血管再通,其疗效优于静脉溶栓;术后联合抗凝及抗血小板治疗对患者的纤溶系统影响不大.     

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension

BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.     

高血压病人纤维蛋白原水平及纤溶系统功能研究

为了解高血压病人的血栓形成倾向,我们随机选取了４１例高血压病人及３４例正常血压者,分别观察了他们的纤维蛋白原及血浆组织型纤溶酶原激活物（ｔＰＡ）抗原及纤溶酶原激活物抑制物－１（ＰＡＩ－１）的含量。结果表明,高血压病人血浆纤维蛋白原水平无明显变化,但ｔＰＡ抗原含量减少,ＰＡＩ－１的水平增加。提示高血压病人存在内源性纤溶功能受损     

Impaired fibrinolysis and insulin resistance in patients with hypertension

Plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) antigens and activities were measured in 28 patients with hypertension and 12 normal controls. Steady state plasma glucose (SSPG) concentrations were also determined after an infusion of somatostatin, insulin and glucose. Patients with hypertension were further subdivided into two groups: insulin resistance (SSPG > 190 mg/dL, n = 14) and no insulin resistance (SSPG < 190 mg/dL, n = 14). As compared to normal controls, hypertensive patients, either with or without insulin resistance, had significant (P < .005) increases in PAI-1 activity (18.6 ± 1.3 ν 8.1 ± 0.8 IU/mL), PAI-1 antigen (31.1 ± 2.0 ν 12.7 ± 0.9 ng/mL) and tPA antigen (15.5 ± 0.9 ν 8.8 ± 0.9 ng/mL), and significant decrease in tPA activity (0.43 ± 0.05 ν 1.02 ± 0.16 IU/mL) than normotensive controls. Furthermore, hypertensive patients with insulin resistance had significantly higher PAI-1 activity (22.0 ± 2.2 ν 15.3 ± 0.8 IU/mL, P = .006) and tPA antigen (17.4 ± 1.2 ν 13.6 ± 1.3 ng/mL, P = .02) than did hypertensive patients without insulin resistance. However, PAI-1 antigen was insignificantly higher (34.1 ± 2.9 ν 28.1 ± 2.4 ng/mL, P = .06) and tPA activity insignificantly lower (0.42 ± 0.08 ν 0.43 ± 0.08 IU/mL, P = .45) in hypertensive patients with insulin resistance than in those without insulin resistance. In addition, PAI-1 activity and tPA antigen were significantly correlated with blood pressure, SSPG, triglyceride, HDL-cholesterol and integrated glucose response to an oral load of 75 g glucose. Thus, patients with hypertension have impaired fibrinolytic activity due to increased PAI-1 when compared to normotensive controls, and the magnitude of this fibrinolytic defect is greater in hypertensive patients who have insulin resistance. Insulin resistance with associated metabolic abnormalities may be one of the causes for impaired fibrinolysis in hypertension.     

氯沙坦对高血压病患者尿白蛋白及纤溶活性的影响

目的　探讨尿白蛋白排泄率与纤溶活性的关系及氯沙坦对其影响。方法　选择 6 2例高血压病伴轻、中度肾功能损害 (肌酐清除率 <70mL/min ,但≥ 30mL/min)患者 ,经随机分为两组分别予氯沙坦 5 0～ 10 0mg/d或卡托普利75～ 15 0mg/d降压治疗 12周。同时选择 2 4例高血压病伴肾功能完全正常 (肌酐清除率≥ 80mL/min)患者作为对照组 ,降压治疗前后分别测定尿白蛋白排泄率 (UAE)、纤溶酶原激活剂活性 (tPA)、纤溶酶原激活抑制剂活性 (PAI)。结果　肾功能异常组UAE、PAI均升高 (P <0 0 1) ,tPA降低 (P <0 0 5 ) ;UAE与tPA ,PAI,PAI/tPA相关系数分别为 0 2 0 (P >0 1)、0 32 (P <0 0 5 )、0 34(P <0 0 1) ,UAE与纤溶活性降低正相关 ;降压治疗后两组均降低UAE、PAI(P <0 0 1) ,卡托普利组还升高tPA(P <0 0 5 )。结论　肾功能异常时纤溶活性降低 ,肾功能损害与纤溶降低有关 ,氯沙坦及卡托普利改善肾功能 ,也改善纤溶活性。     

厄贝沙坦与非洛地平对原发性高血压纤溶系统影响的比较

目的 :通过比较厄贝沙坦和非洛地平对原发性高血压 (EH)患者纤溶系统的影响 ,探讨在改善EH纤溶障碍方面厄贝沙坦是否优于非洛地平。方法 :5 3例 1、2级EH患者随机分为厄贝沙坦组 2 8例 (厄贝沙坦15 0mg/d)和非洛地平组 2 5例 (非洛地平 5mg/d) ,共服药物 2周 ,观察治疗前后血压、血浆组织型纤溶酶原激活物 (tPA)及其抑制物 (PAI 1)含量、D 二聚体 (D D)和血管性血友病因子 (vWF)水平的变化。结果 :两组患者的基本资料差异无显著性意义 (P >0 .0 5 ) ,两组患者治疗后血压均显著性下降 (P <0 .0 1) ,但两组之间治疗前后血压相比差异无显著性意义 (P >0 .0 5 )。治疗后两组PAI 1、vWF和D D水平均显著下降 (P <0 .0 5 ) ,tPA和tPA/PAI 1比值明显升高 (P <0 .0 5 )。两组之间治疗前的tPA、PAI 1、D D和vWF含量差异均无显著意义 ,治疗后的D D和vWF水平差异也无显著性意义 ,但PAI 1含量在厄贝沙坦组减少更明显 (P <0 .0 5 ) ,tPA和tPA/PAI 1比值在厄贝沙坦组增加更显著 (P <0 .0 5 )。结论 :厄贝沙坦和非洛地平均能有效改善EH的纤溶障碍 ,但厄贝沙坦优于非洛地平     

氯沙坦和依那普利对心肌梗死后纤溶-凝血功能的影响

目的　探讨氯沙坦和依那普利对急性心肌梗死 (AMI)患者纤溶 凝血功能的影响。方法　将 41例AMI患者随机分为氯沙坦组、依那普利组和对照组 ,以发色底物法和ELISA法测定三组患者入院即刻、发病 2周、2个月的血浆PAI 1活性、纤溶酶原激活物 (tPA)抗原水平和血管血友病病因子(vWF)含量。结果　与对照组相比 ,氯沙坦组 2周和 2个月时的PAI 1活性分别减低 2 2 % (P <0 0 1)和 18% (P <0 0 5 ) ,tPA抗原水平分别减低 32 % (P <0 0 1)和 2 5 % (P <0 0 5 ) ;依那普利组相应分别减低 2 8% (P <0 0 1)和 2 1% (P <0 0 5 ) ,tPA抗原水平分别减低 38% (P <0 0 1)和 2 9% (P <0 0 5 ) ;两个治疗组之间差异无显著性。两种药物对vWF含量均无影响。结论　氯沙坦和依那普利可改善心肌梗死后的纤溶功能 ,长期应用这两种药物可能会降低心肌梗死后发生急性心脏事件的危险。     

Impact of the therapy by renin-angiotensin system targeting antihypertensive agents perindopril versus telmisartan on prothrombotic state in essential hypertension

The aim of the study was to investigate the effect of therapy by perindopril or telmisartan on endothelial/platelet function and on coagulation/fibrinolysis in 20 and 16 hypertensive patients, respectively. The measurements were carried out before and after 1 month of therapy. Both systolic blood pressure and diastolic blood pressure were reduced (P<0.001) or normalized due to each therapy. Plasma thrombomodulin (TM) and von Willebrand factor (vWF) as indicators of endothelial dysfunction, plasma beta-thromboglobulin (betaTG), platelet factor 4 (PF4), soluble P-selectin (sPsel) and soluble glycoprotein V (sGpV) as indicators of in vivo platelet activation, plasminogen activator inhibitor type 1 (PAI-1) antigen and tissue type plasminogen activator (tPA) antigen as markers of fibrinolytic activity, soluble endothelial protein C receptor (sEPCR) as a new marker of hypercoagulation and fibrinogen level as a known risk factor for vascular changes were investigated. A decrease of plasma vWF, sPsel, sGpV, PAI-1 and tPA antigen level (P<0.05, respectively) after 1 month of therapy by perindopril was observed. On the other hand, a decrease of plasma sEPCR and fibrinogen level (P<0.05, respectively) after 1 month of therapy by telmisartan was found. We failed to find changes of plasma TM, betaTG and PF4 due to any therapy investigated. The additional beneficial 'antithrombotic' effects of the renin-angiotensin system targeting agents (vasculoprotective, anti-platelet and profibrinolytic effects of perindopril and anticoagulant/rheological effects of telmisartan) may be important in terms of the favourable role of antihypertensive drugs in cardiovascular morbidity.     

持续气道正压通气对OSAHS患者血管内皮细胞及纤溶系统的影响

为探讨经鼻持续气道正压通气（nCPAP)治疗前后阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者血管内皮细胞及纤溶系统的变化及临床意义，选择年龄，性别，体重指数（BMI）无明显差异的OSAHS患者38例和健康者对照组32例，用多导睡眠呼吸监测仪进行监测，以凝固法测定纤维蛋白原（Fg），发色底物法测组织纤溶酶原激活物活性（tPA：A）、纤溶酶原激活物抑制物－1活性（PAI－1：A），酶联免疫法测vonWillebrand因子（vWF)、组织纤溶酶原激活物抗原（tPA:Ag）、纤溶酶原含量（PLg:Ag)和纤溶酶原激活物抑制物－1含量（PAI－1：Ag）。结果OSAHS组与对照组比较，vWF,Fg,tPA:Ag、PAI－1：A明显升高（P分别＜0．01，0．001，0．001，0．01），PLg:Ag、tPA:A、tPA:Ag、最低血氧饱和度（SaO2low)明显降低（P分别＜0．01，0．001，0．001，0．01).nCPAP治疗后与治疗前比较，vWF,Fg,PAI-1:Ag,PAI-1:A明显降低（P分别＜0．05，0．01，0．01，0．01），PLg:Ag,tPA:A,tPA:Ag，最低SaO2明显升高（P分别＜0．05，0．001，0．001，0．01）。提示OSAHS患者血管内皮细胞损伤，凝血功能增强，纤溶系统功能减弱;nCPAP治疗能部分纠正各指标的异常。