咪达普利和厄贝沙坦对早期自发性高血压大鼠凝血和纤溶系统的影响

目的观察咪达普利(imidapril)和厄贝沙坦(irbesartan)在降压同时,对早期雄性自发性高血压大鼠(SHR)血浆凝血酶原时间(PT)、纤维蛋白原含量( FIB)、组织型纤溶酶原激活物活性(t-PAA)、纤溶酶原激活物抑制剂活性( PAIA)和α2-纤溶酶抑制物活性(α2-PIA)的影响.方法15周龄雄性SHR 30只随机分为三组,咪达普利组给含imidapril的水 3 mg·kg-1·d-1;厄贝沙坦组给含irbesartan的水50 mg·kg-1·d-1;SHR对照组和同龄雄性Wistar Kyoto(WKY)正常血压对照组10只以等量蒸馏水代替;采用一期法检测血浆PT,采用凝血酶法检测血浆FIB,采用发色底物法检测血浆t-PAA、PAIA和α2-PIA.结果与WKY组比较,SHR组血浆FIB显著增高(P<0.01),α2-PIA显著降低(P<0.01).咪达普利组和厄贝沙坦组经过三个月治疗血压明显降低(P<0.01),FIB显著降低(P<0.01),α2-PIA显著增高(P<0.01).结论(1) 早期雄性SHR血管内凝血与纤溶并存,提示早期雄性SHR已处于慢性过代偿型弥散性血管内凝血(DIC) 凝溶期,因而有血栓栓塞和/或出血的危险性;(2) 咪达普利和厄贝沙坦对早期雄性SHR的干预能逆转SHR慢性隐性DIC所致的血栓前状态(PTS)和动脉粥样硬化(AS),改善其已受损的凝血和纤溶系统.     

氨氯地平和厄贝沙坦对自发性高血压大鼠凝血和纤溶系统的影响(摘要)

目的　检测自发性高血压大鼠的凝血和纤溶状态并以此为依据合理选用能改善其凝血和纤溶状态的抗高血压药物。方法　15周龄雄性自发性高血压大鼠 2 4只随机分为三组 ,①氨氯地平组 8只 ,给含amlodipine 5mg (kg·d)的水 ;②厄贝沙坦组 8只 ,给含irbesartan 5 0mg (kg·d)的水 ;③自发性高血压大鼠对照组和雄性WistarKyoto(WKY)正常血压对照组各 6只 ,以等量蒸馏水代替 ;以上疗程均为 8周。于试验前、喂养 8周后测尾动脉收缩压后于尾动脉取血测定血清一氧化氮及其合酶水平 ,同时取抗凝血检测血浆组织型纤溶酶原激活物 (t PA)活性、纤溶酶原激活物抑制剂 1(PAI 1)活性。结果　与WKY组比较 ,自发性高血压大鼠组血浆PAI 1活性显著增高 (1.12± 0 .2 2比 0 .83± 0 .31,P <0 .0 1) ,t PA和NOS活性及NO水平显著降低 (0 .32± 0 .0 7,5 3.2± 8.7,32 .5± 4 .4比 0 .4 6± 0 .13,6 4 .4± 10 .1,4 4 .5± 7.4 ,P均 <0 .0 1) ,t PA和NOS活性及NO水平显著增高 (P <0 .0 1)。结论　①自发性高血压大鼠血管内凝血与纤溶并存 ,因而有血栓栓塞和 或出血的危险性 ;②氨氯地平和厄贝沙坦对自发性高血压大鼠的干预能逆转自发性高血压大鼠的血栓前状态 (PTS) ,改善其已受损的凝血和纤溶系统。     

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     

厄贝沙坦对高血压并发充血性心力衰竭患者凝血-纤溶系统及心功能的影响

将100例高血压并充血性心力衰竭患者随机分为观察组及对照组各50例。观察组口服厄贝沙坦150mg,1次/d,连用4周;对照组口服卡托普利25mg,3次/d,连用4周。用药前后测量血压,采用一期法检测血浆凝血酶原时间(PT),凝血酶法检测血浆纤维蛋白原(FIB),发色底物法检测血浆组织型纤溶酶原激活物(t-PA)、纤溶酶原激活抑制物-1(PAI-1)水平,行超声心动图计算左室射血分数(LVEF)和舒张早期最大心室充盈速度值/舒张晚期最大心室充盈速度值(E/A值),评定心功能变化。结果治疗4周后两组血压及FIB、PAI-1水平均降低(P均<0.01),t-PA、LVEF及E/A值明显升高(P均<0.01);但观察组分别显著低于和高于对照组(P<0.01)。证实厄贝沙坦可改善高血压合并充血性心衰患者凝血-纤溶系统功能,逆转高血压、心力衰竭所致的血栓前状态;改善心脏收缩和舒张功能,缓解心衰症状,其疗效优于卡托普利。     

雄性自发性高血压大鼠代谢综合征相关指标及药物干预的研究

目的:探讨早期雄性自发性高血压大鼠(SHR)血清尿酸(UA)和血脂代谢异常在高血压靶器官损害进程中的作用,并观察厄贝沙坦(irbesartan)对血尿酸和血脂代谢的影响。方法:对象为15周龄雄性SHR20只和正常雄性同龄WistarKyoto(WKY)大鼠10只。将SHR随机分为两组:厄贝沙坦治疗组(按厄贝沙坦50mg/kg.d从饮水给药);SHR阳性对照组。后者与WKY正常对照组喂以等量蒸馏水代替。实验于三个月后停药,测体重和血压,检测血清UA、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)值。结果:实验三个月后,与WKY组比较,SHR组UA水平显著增高(P<0.05),血压和TG水平显著增高(P<0.01);与SHR组比较,厄贝沙坦组血压和TG水平显著降低(P<0.01),UA水平显著降低(P<0.05)。结论:高血压病早期已经存在着高尿酸血症和血脂异常等代谢异常的临床征象,厄贝沙坦既具有降低TG又具有降低UA的作用,可能有抗动脉粥样硬化和肾保护作用。     

厄贝沙坦对高血压患者纤维蛋白溶解障碍的影响

目的　观察厄贝沙坦对高血压患者纤溶障碍的影响。方法　观察 2 8例 1、2级原发性高血压病人用厄贝沙坦治疗 2周前后血压、心率、血浆纤溶性指标 (t PA抗原、PAI抗原和 D-二聚体 )和血管性血友病因子 (v WF)水平的变化 ,并与 2 1例健康对照组比较。血液指标测量均采用酶联免疫吸附双抗体夹心法。结果　 2 8例病人经厄贝沙坦降压治疗 2周后 ,血压明显下降 (P<0 .0 1) ,而心率无明显变化 (P>0 .0 5 )。 2 8例病人治疗前血浆 PAI- 1、D-二聚体和v WF水平明显高于对照组 (P<0 .0 1) ,治疗后明显下降 (P<0 .0 1) ;2 8例病人治疗前 t PA抗原 ,t PA/ PAT- 1比值明显低于对照组 (P<0 .0 1) ,治疗后明显增加 (P<0 .0 1)。结论　 AT1受体阻滞剂厄贝沙坦可明显改善高血压病患者纤溶障碍 ,其作用机制可能部分与改善内皮功能有关     

替米沙坦对高血压大鼠纤溶功能的作用机制

目的探讨血管紧张素Ⅱ(AngⅡ)促血管内皮细胞和平滑肌细胞合成与分泌纤溶酶原激活物抑制物1(PAI1)的受体和受体后信号转导途径以及替米沙坦对高血压大鼠纤溶参数的影响和可能机制。方法腹主动脉部分缩窄构建高血压大鼠模型,随机分成高血压组和替米沙坦组(3mg/·d)6周,另设假手术组为对照组。检测大鼠血浆与主动脉组织匀浆中AngⅡ含量,血浆与主动脉孵育液中纤溶酶原激活物(tPA)、PAI1活性,血管内皮细胞、平滑肌细胞胞外信号调节激酶(ERK)和血管紧张素Ⅱ1型受体(AT1R)蛋白的表达。结果①高血压组血浆AngⅡ含量、血浆PAI1活性、血管平滑肌细胞ERK蛋白及AT1R蛋白的表达4者之间显著正相关(r=0.89～0.96,P<0.01～0.001)。主动脉匀浆AngⅡ含量、主动脉孵育液PAI1活性、血管平滑肌细胞ERK蛋白及AT1R蛋白的表达4者之间显著正相关(r=0.86～0.96,P<0.01～0.001)。②与高血压组比较,替米沙坦能明显抑制主动脉分泌PAI1的能力(P<0.05),降低血浆PAI1活性(P<0.05),升高血浆与主动脉孵育液中tPA活性、tPA/PAI1值(P均<0.05),明显改善纤溶参数。③替米沙坦组ERK和AT1R在血管内皮细胞和平滑肌细胞的表达较高血压组明显减少(P均<0.05)。结论替米沙坦抑制血管内皮细胞、血管平滑肌细胞ERK和AT1R的表达,抑制AngⅡ引起的PAI1合成增加,可能是其改善纤溶功能的机制。     

自发性高血压大鼠相关指标的昼夜节律变化及厄贝沙坦的干预作用

目的研究自发性高血压大鼠（SHR）的血压、内皮功能、纤溶活性的昼夜节律变化及厄贝沙坦的干预作用。方法30只SHR大鼠分别于3啪、9am、3pm、9pm测量血压,硝酸还原酶法测定一氧化氮（NO）、一氧化氮合酶（NOS）,发色底物法测定蛋白C（PC）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）活性。喂食厄贝沙坦4周后复查上述指标。结果所有动物血压、心率、NO、NOS、纤溶活性均存在昼夜节律变化;采用厄贝沙坦干预后上述指标的昼夜节律无明显变化;同一时点血压、心率、PAI-1降低,NO、NOS、PC、t-PA升高（P均〈0．01）。结论SHR的血压、NO、NOS、纤溶活性存在昼夜节律变化;厄贝沙坦可降低SHR大鼠血压,改善内皮功能,调节纤溶活性,但对其昼夜节律无明显影响。     

纤溶酶原激活物抑制剂—1与代谢综合征

血浆纤溶酶原激活物抑制剂－1（plasminogen activator inhibitor-1,PAL-1)主要与组织型纤溶酶原和尿激酶型纤溶酶原激活物结合,起着抑制纤溶活性的作用。代谢综合征包括高血压,糖尿病以及血指异常,胰岛素抵抗和肥胖,与PAI－1有着密切联系,,两者共同作用时,容易引起动脉粥样硬化以及其他血管性疾病,降低PAI－1和改善代谢紊乱的措施将可以预防或减少上述疾病的发生。     

厄贝沙坦和培哚普利对轻中度原发性高血压凝血纤溶系统的影响

目的观察厄贝沙坦和培哚普利在降压的同时,对原发性高血压凝血纤溶系统的影响.方法测定48例轻中度原发性高血压患者及23例对照组血浆纤维蛋白原(Fbg)、D-二聚体(D-D)、抗凝血酶Ⅲ(AT-Ⅲ)水平.将48例轻中度高血压患者随机分成2组,厄贝沙坦组22例,150 mg/d口服;培哚普利组26例4 mg/d口服,治疗后6周测Fbg、D-D、AT-Ⅲ.结果高血压组治疗前Fbg、D-D显著高于对照组(P均＜0.01),AT-Ⅲ低于对照组(P＜0.05).药物治疗后2组Fbg、D-D均较用药前降低,差异有显著性(P均＜0.01),AT-Ⅲ均升高(P＜0.05).结论厄贝沙坦和培哚普利在控制血压的同时能改善高血压患者的高凝和继发性纤溶亢进状态.     

Activated factor V is a cofactor for the activation of factor XI by thrombin in plasma

The mechanism by which the intrinsic pathway of coagulation contributes to physiological hemostasis is enigmatic. Thrombin activates factor XI, a key zymogen in this pathway, which leads to increased thrombin generation. As thrombin-dependent activation of factor XI in vitro is relatively inefficient, we hypothesized that a physiological cofactor supports this reaction in a plasma environment. We therefore investigated whether the cofactors of coagulation, activated factor V, activated factor VIII, high-molecular weight kininogen, or protein S, influenced activation of factor XI by thrombin. Only activated factor V stimulated activation of factor XI by thrombin in a purified system. Binding studies demonstrated that factor XI specifically interacts with both factor V and factor Va through multiple binding sites. We further investigated this cofactor function of activated factor V in plasma. Depletion of factor V, or the addition of activated protein C, decreased the activation of the intrinsic pathway by thrombin in plasma. However, activated protein C did not exert this effect in the plasma of a homozygous carrier of the prothrombotic factor V Leiden mutation. In conclusion, we propose a role for (activated) factor V as a cofactor in the activation of factor XI by thrombin. These findings offer insights into the coagulation system in both health and disease.     

Recent developments in our understanding of the antiphospholipid syndrome

The antiphospholipid syndrome is an autoimmune disease that manifests clinically as recurrent thrombotic complications or foetal losses and serologically with elevated levels of antiphospholipid antibodies in the plasmas of these patients. The term 'antiphospholipid syndrome' is confusing, because the auto-antibodies are not directed against phospholipids but towards a plasma protein, β(2) -glycoprotein I. For many years, the reason why auto-antibodies against β(2) -glycoprotein I were pro-thrombotic was unclear, because β(2) -glycoprotein I seems to be an obsolete protein in our circulation. Human and mice deficient in this protein do not express a clear phenotype. Recent studies on the structure and function of β(2) -glycoprotein I have provided novel insights into the importance of this protein in physiology and its role in the pathology of the antiphospholipid syndrome.     

重度失血性休克后凝血机制的异常改变及原因分析

目的:观察分析重度失血性休克后凝血机制的变化及其处理。方法:重度失血性休克患者17例,给予生命体征监测,观察其全身及手术伤口局部出血情况,定时抽取血样做血常规、肝肾功能及凝血功能测定,对符合凝血功能障碍诊断标准者均给予输血及补充凝血因子、止血及积极治疗原发病等处理。结果:所有患者均在休克后发生全身多处出血或渗血;血红蛋白显著低于正常值,血小板明显减少;转氨酶异常升高;凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）时间延长,国际标准化比值（INR）显著高于正常值,凝血酶原活动度（AT）显著低于正常值（与正常值比较,均P<0.01）。所有患者经过治疗后,出血现象均得到控制,凝血机制相关指标均恢复正常或接近正常范围（与治疗前比较,均P<0.05或P<0.01）,同时转氨酶也有显著下降（与治疗前比较,均P<0.01）。结论:重度失血性休克后均可能发生凝血功能障碍,经及时给予输血、补充凝血因子、止血及原发病治疗后,均可得到有效的控制。     

他汀类药物调节凝血功能及其机制

已经证实他汀类药物的多效性对心血管具有明显的保护作用,他汀类药物从多个水平调节凝血级联反应,包括抑制凝血酶催化的凝血反应,以及增强凝血抑制物的抗凝作用,从而起到抗血栓作用。他汀类药物的多效性大多与其降低胆固醇的作用无关,其调节凝血级联反应的机制主要是抑制信号蛋白的异戊二烯化。     

Prognostic role of screening tests of haemostasis and underlying diseases in acute disseminated intra-vascular coagulation in adults

Summary. The significance of precipitating causes of acute disseminated intra-vascular coagulation (DIC) and the severity of derangement of haemostasis based on laboratory investigations carried out initially were evaluated in 98 patients and was related to the fatal outcome in them. It was seen that septicaemia was the commonest precipating cause. Survival was better in patients in whom DIC was precipitated by obstetric causes compared with those with septicaemia (P < 0.01). Death was also more frequently associated in patients with higher prothrombin time (PPT) ratio (> 1.5) and/or higher activated partial thromboplastin time (APTT) ratio (> 2.5) as compared to their lower values (P < 0.01 each). Death occurred in all the seventeen patients in whom septicaemia was present along with PPT ratio of > 1.5. It is concluded that deranged haemostasis and presence of septicaemia both independent of each other, contribute to the fatal outcome in acute DIC. Combination of both is associated with poorest prognosis.     

Coagulation abnormalities in diabetic coma before and 24 hours after treatment

Summary A coagulation screen consisting of measurement of the prothrombin time, thrombin time, kaolin cephalin clotting time, platelet count, plasma fibrinogen level, fibrin degradation products and ethanol gelation test was performed on 24 patients with impairment of consciousness due to acute diabetic metabolic decompensation at the start of treatment and 24 hours later. 22 out of 24 patients showed at least one coagulation abnormality on admission of which the commonest were a prolonged prothrombin time, shortened kaolin cephalin clotting time and raised plasma fibrinogen level. After 24 hours of treatment these values were more normal but 20 out of 22 patients still displayed some abnormality. 15 patients had two or more coagulation abnormalities on admission including 3 patients with haematological abnormalities suggestive of disseminated intravascular coagulation. This group was older and had higher blood ureas than those with fewer abnormalities, but plasma glucose, sodium, potassium and bicarbonate levels were similar in both groups of patients. All 5 patients with hyperosmolar non-ketotic coma and all 3 patients who died without recovering consciousness had two or more coagulation abnormalities on admission.     

New products for the treatment of haemophilia

Current developments in haemophilia therapy are directed at two therapeutic targets: reduction of injection frequency and reduction or bypassing of inhibitors. A variety of new molecules addressing these aims are now completing clinical trials and are ready to enter clinical use. First amongst these are modified Factor VIII (FVIII) and Factor IX (FIX) molecules with extended half‐lives. FIX modifications have achieved 5‐fold prolongation of half‐life whilst effects on FVIII have been more modest, at less than two‐fold. We now face the problem of integrating these into clinical practice. Other approaches have generated chemically modified FVIII molecules with altered activation profiles. An alternative way of correcting the haemophilia defect is to reduce the activity of natural anticoagulants in an attempt to restore the balance of haemostasis. These methods are also giving promising results but, as with all new approaches, it will be some while before they all find their place in practice.