活血化瘀法治疗肾小球疾病31例体会

肾小球疾病的病因,以免疫炎症为主,也有凝血、纤溶系统的参与.由于凝血因子作用增强,抗凝活性降低,纤溶抑制因子增加,造成高凝状态,影响疾病的转归和预后.     

溃疡性结肠炎对凝血-纤溶系统激活现象的探讨

目的:通过对活动期和缓解期溃疡性结肠炎(UC)患者凝血和纤溶系统各指标的检测和对比,探讨肠炎对凝血-纤溶系统的激活作用。方法:以20名缓解期溃疡性结肠炎患者为对照,检测20名活动期溃疡性结肠炎患者体内凝血和纤溶系统各指标,包括血小板计数、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT)、凝血因子Ⅻ、Ⅺ、Ⅹ、Ⅸ、Ⅷ、Ⅶ、Ⅴ、Ⅱ,纤维蛋白原和D二聚体(D-D)。结果:活动期溃疡性结肠炎患者体内凝血因子Ⅺ、Ⅹ、Ⅸ、Ⅷ、Ⅴ、Ⅱ因子以及血浆纤维蛋白原、D-二聚体水平显著高于非活动期患者,其他指标没有显著差别。结论:活动期溃疡性结肠炎患者凝血-纤溶系统处于激活状态,提示肠炎可以激活凝血-纤溶系统。     

糖尿病肾病致凝血异常的研究

糖尿病(DM)已成为世界性的常见病,其发病率高,并且随着生活水平的改善,其发病率必然还会进一步加剧。血管病变是DM的重要并发症之一,糖尿病肾病(DN)是糖尿病常见且严重的微血管并发症,与血栓形成密切相关。糖尿病肾病的进展伴随着体内凝血活性和抗凝活性的失调,同时激活自身免疫系统,发生炎症反应。炎症应答过程中释放的炎症因子损伤肾小球内皮细胞,导致抗凝活性减弱。DN患者体内血细胞激活,微粒形成增多会加强凝血活性。此外,纤溶酶抑制剂(PAI-1)与纤溶酶激活剂(t PA)的失衡会引起纤溶系统紊乱。这三个方面引起DN患者体内的高凝状态加重,并因此加速肾功能恶化,导致肾小球率过滤降低,系膜基质增多,最终引起肾小球硬化及终末期肾脏疾病。本文就糖尿病肾病致凝血异常的发生机制做一综述。     

赤爱胜蚯蚓(Eisenia Foetida Sarigny)纤溶酶的研究Ⅱ药理学作用

对蚯蚓纤溶酶进行了哈白兔体内、体外溶栓、抗凝试验,分别以蛇毒抗栓酶和尿激酶不同剂量组作对照试验,均有显著的溶解血栓功能.另外,蚯蚓纤溶酶溶解天然血块,对纤维蛋白原含量及凝血时间影响的药理学试验,结果证明蚯蚓纤溶酶具有溶栓与抗凝作用.     

烙铁头蛇毒对体外血凝及纤溶的影响

行体外血凝及纤溶观察结果表明：①烙铁头蛇毒能明显延长凝血活酶时间（ＰＴＴ）、凝血酶原时间（ＰＴ）及蝰蛇毒磷脂时间（ＲＶＶＣＴ）,显示出较强的抗凝活性;②对人纤维蛋白原及纤维蛋白有较强的溶解作用,这种作用不完全是单一的活化素样作用,还有脆浆素样作用     

接触系统生物学意义的再认识

目前,凝血学说发放发生了概念性改变,认为体风凝血过程分为两个阶段?组织因子途径凝血过程的启动,以因子Ⅸ（ＦⅨ）为起点的内在途径凝血过程的放大,而接触系统并不参与体内凝血过程。已有资料表明,接触系统是一个重要的血管生物学调制 主要作用包括调整血管紧张度、抑制血小板活化、促进纤溶、抑制粘附以及促进炎病等。它的改变与败血症、血栓性疾病等病变过程密切相关。     

血管内皮细胞的抗凝和纤溶系统及与肿瘤转移的关系

血管内皮细胞呈扁平状态覆盖于整个血管内壁,由其组成的内皮是介于血液、淋巴液与组织之间的屏障,与血液有相容性,有隔开血液和组织的作用,其主要特点有;(1)抗凝性;(2)纤溶性;(3)选择性通透性;(4)血管紧张调节;(5)能分泌多种因子,等等,在维持血液循环正常功能过程中有着重要作用。本文着重讨论内皮细胞的抗凝系统和纤溶系统及其与肿瘤转移的关系。     

沙棘油对实验性血栓形成及凝血系统的影响

沙棘油能使实验性血栓形成延迟,具有预防血栓形成的作用。沙棘油有一定的抗凝作用,主要参与内源性凝血系统;且有促纤溶作用,明显降低纤维蛋白原含量,使血浆鱼精蛋白副凝试验呈阳性反应。     

高胆固醇饲料对雄兔凝血和纤溶系统活性的影响

目的:探讨高胆回醇饲料喂养对兔血液凝血和纤溶系统活性的影响.方法:14只10～12周龄的健康雄性新西兰家兔,随机分为高胆固醇饲料喂养组(高胆固醇组)和普通饲料喂养组(对照组).高胆固醇组以含1%胆固醇的饲料喂饲,每天100 g,自由饮水,对照组给予不合胆固醇的普通饲料喂养,共喂养14周.所有雄兔均分别于高胆固醇饲料喂养前及不同饲料喂养后12周采耳缘静脉血分别测定血脂水平变化及血液凝血和纤溶系统活性变化.结果:①与对照组及基础值相比,高胆固醇组雄兔血中的甘油三酯、总胆固醇、低密度脂蛋白、脂蛋白(a)、载脂蛋白B水平显著升高;②高胆固醇组雄兔血小板活性显著增强、凝血酶原时间及活化部分凝血酶时间缩短、纤维蛋白原含量增加;③高胆固醇组纤溶酶原活性、α2-抗纤溶酶活性较普通组增强.结论:高胆固醇饮食不仅能直接导致高脂血症的形成,还可显著增强血液凝血活性和抑制血液纤溶活性,促进动脉粥样硬化的发生发展.     

超高龄患者填充骨水泥型人工股骨头置换术后的凝血功能变化及意义

目的：观察骨水泥填充对人工股骨头置换术术后超高龄老年患者凝血系统的影响。方法：选择80岁以上骨水泥型人工股骨头置换术患者29例,于术前、术后当天及术后第3天空腹抽取静脉血,测定凝血功能相关指标,包括凝血酶原时间（PT）、部分凝血活酶时间（APTT）、凝血酶时间（TT）、凝血酶原活动度（PTA）、国际标准化比值（INR）、纤维蛋白原（FIB）、D二聚体（DD）、抗凝血酶Ⅲ（ATⅢ）、血小板（PLT）水平,并对结果进行比较分析。结果：患者术后当天FIB、DD、显著升高（P〈0.05）,ATⅢ降低（P〈0.05）,提示高凝状态,且纤溶亢进,此时段TT、PT延长（P〈0.05）,血小板明显降低,提示存在出血风险;术后第3天TT、PT显著延长（P〈0.05）,ATⅢ恢复到术前水平,FIB,DD水平较手术后当天下降,提示术后第3天有明显的出血倾向,凝血与纤溶系统逐渐恢复平衡。结论：骨水泥型人工股骨头置换术对80岁以上超高龄患者凝血功能有显著影响,术后当天高凝状态、纤溶亢进,存在潜在出血风险,术后第3天有明显出血倾向,提示高龄患者术后应适当补充凝血因子且须谨慎使用抗凝药物。     

A complex of heparin with the peptide Arg-Pro-Gly-Pro and its anticoagulative,fibrinolytic, and hypoglycemia effects

Heparin was bound to the arginine-containing peptide Arg-Pro-Gly-Pro with the molar ratio of heparin to the peptide 1 : 1. The complex compound showed antiplatelet, anticoagulative, and fibrin-depolymerization activities. In an in vivo study, in type 2 diabetes progression, a 5-fold intranasal administration of the compound restored both impaired insular and anticlotting functions in rats. Furthermore, blood fibrinolytic and anticoagulative activities increased.     

嵌合体纤溶酶的研究进展

嵌合体纤溶酶是采用基因重组技术或化学偶联的方法将纤溶酶与其它的功能多肽(舍有酶原结构域,具有抗凝血酶、抗血小板聚集活性,能特异识别纤维蛋白的多肽)结合起来所形成的嵌合体蛋白质．它尽可能地保留了分子中每一组分的生物活性,增强了纤溶酶的溶栓功效,较大程度地克服了临床溶栓药物在某些方面的不足,是目前溶栓药物研究领域中的热点。     

Pathophysiology of thrombophilic states

The coagulation system can be considered as a balance in which clotting and fibrinolysis have to be in a state of equilibrium. Increased fibrin formation or decreased fibrinolysis can predispose to thromboembolic diseases. Derailments in the clotting system leading to thrombosis center around the regulatory mechanisms, antithrombin III, protein C, protein S and possibly heparin cofactor II. Many cases of congenital or acquired deficiencies or abnormalities or antithrombin III, protein C and S have been described, all predisposing to thrombotic events. Alterations of the fibrinolytic system can also be associated with thromboembolisms. In particular, abnormalities of plasminogen, tissue plasminogen activator release and elevated tissue plasminogen activator inhibitor levels seem to be associated with thromboses. Conceivably also factor XIIa (Hageman factor) and prekallikrein deficiencies, when associated with thrombosis, exert their mechanism through the fibrinolytic system. Finally, about 50% of patients with lupus anticoagulant seem to suffer from thromboembolic disorders. The pathophysiology of this particular association is not known with certainty. Undoubtedly, there will be more disturbances discovered in the hemostasis system that are associated with increased intravascular fibrin formation. The understanding of these derailments is at this time only in its earliest stages of development.     

Genome-editing technologies for gene correction of hemophilia

Hemophilia is caused by various mutations in blood coagulation factor genes, including factor VIII (FVIII) and factor IX (FIX), that encode key proteins in the blood clotting pathway. Although the addition of therapeutic genes or infusion of clotting factors may be used to remedy hemophilia’s symptoms, no permanent cure for the disease exists. Moreover, patients often develop neutralizing antibodies or experience adverse effects that limit the therapy’s benefits. However, targeted gene therapy involving the precise correction of these mutated genes at the genome level using programmable nucleases is a promising strategy. These nucleases can induce double-strand breaks (DSBs) on genomes, and repairs of such induced DSBs by the two cellular repair systems enable a targeted gene correction. Going beyond cultured cell systems, we are now entering the age of direct gene correction in vivo using various delivery tools. Here, we describe the current status of in vivo and ex vivo genome-editing technology related to potential hemophilia gene correction and the prominent issues surrounding its application in patients with monogenic diseases.     

Cholesterol diet enhances daily rhythm of Pai-1 mRNA in the mouse liver

Myocardial infarction frequently occurs in the morning, a phenomenon in part resulting from the downregulation of fibrinolytic activity. Plasminogen activator inhibitor-1 (PAI-1) is a key factor behind fibrinolytic activity, and its gene expression is controlled under the circadian clock gene in the mouse heart and liver. Hypercholesterolemia has been associated with impaired fibrinolysis due to enhanced PAI-1 activity, which has also been implicated in atherosclerosis. The aim of this study was to decipher whether the Pai-1 gene is still expressed daily with hypercholesterolemia. Hypercholesterolemia (1% cholesterol diet) did not significantly affect the daily expression of clock genes (Per2 and Bmal1) and clock-controlled genes (Dbp and E4bp4) in the liver (P > 0.05); however, daily expression of the Pai-1 gene and Pai-1 promoter regulating factor genes such as Nr4a1 was significantly upregulated (P < 0.01). Daily restricted feeding for 4 h during the day reset the gene expression of Per2, Pai-1, Nr4a1, and Tnf-alpha. Lesion of the suprachiasmatic nucleus, the location of the main clock system, led to loss of Per2 and Pai-1 daily expression profiles. In the present experiments, we demonstrated that hypercholesterolemia enhanced daily expression of the Pai-1, Tnf-alpha, and Nr4a1 genes in the mouse liver without affecting clock and clock-controlled genes. Therefore, the risk or high frequency of acute atherothrombotic events in the morning still seems to be a factor that may be augmented under conditions of hypercholesterolemia.     

Polyphosphate and omptins: novel bacterial procoagulant agents

Derangement of the blood clotting system contributes strongly to multiple organ failure in severe sepsis. In this review, we examine two microbial modulators of the clotting system: polyphosphates and omptins. Polyphosphates are linear polymers of inorganic phosphate that are abundant in the acidocalcisomes of prokaryotes and unicellular organisms as well as in the dense granules of human platelets. Polyphosphates modulate haemostasis by: (1) triggering clotting via the contact pathway; (2) accelerating the activation of coagulation factor V (a key cofactor in blood clotting) and (3) causing fibrin to form clots whose fibrils are thicker and more resistant to fibrinolysis. While polyphosphates are found in all prokaryotes, omptins have a more limited distribution among certain Gram-negative species. Omptins are outer membrane aspartyl proteases which were recently found to proteolytically inactivate tissue factor pathway inhibitor (TFPI), the main inhibitor of the initiation phase of blood clotting. Omptin activity against TFPI requires lipopolysaccharide without O-antigen (rough LPS) such as is found on the surface of Yersinia pestis, the etiologic agent of plague. Interestingly, expression of Pla, the Yersinia pestis omptin, has a demonstrated virulence role in converting plasminogen into the fibrinolytic enzyme plasmin, which would seemingly antagonize any procoagulant effect of TFPI inactivation. However, since the rate of TFPI inactivation is much higher than the rate of plasminogen activation, we suggest that Pla may have a dual function in supporting the bubonic form of plague which is unique to Yersinia pestis.     

From selective substrate analogue factor Xa inhibitors to dual inhibitors of thrombin and factor Xa. Part 3

Highly potent and selective substrate analogue factor Xa inhibitors were obtained by incorporation of non-basic or modestly basic P1 residues known from the development of thrombin inhibitors. The modification of the P2 and P3 amino acids strongly influenced the selectivity and provided potent dual factor Xa and thrombin inhibitors without affecting the fibrinolytic enzymes. Several inhibitors demonstrated excellent anticoagulant efficacy in standard clotting assays in human plasma.     

Genomic Evidence for a Simpler Clotting Scheme in Jawless Vertebrates

Mammalian blood clotting involves numerous components, most of which are the result of gene duplications that occurred early in vertebrate evolution and after the divergence of protochordates. As such, the genomes of the jawless fish (hagfish and lamprey) offer the best possibility for finding systems that might have a reduced set of the many clotting factors observed in higher vertebrates. The most straightforward way of inventorying these factors may be through whole genome sequencing. In this regard, the NCBI Trace database ( http://www.ncbi.nlm.nih.gov/Traces/trace.cgi ) for the lamprey (Petromyzon marinus) contains more than 18 million raw DNA sequences determined by whole-genome shotgun methodology. The data are estimated to be about sixfold redundant, indicating that coverage is sufficiently complete to permit judgments about the presence or absence of particular genes. A search for 20 proteins whose sequences were determined prior to the trace database study found all 20. A subsequent search for specified coagulation factors revealed a lamprey system with a smaller number of components than is found in other vertebrates in that factors V and VIII seem to be represented by a single gene, and factor IX, which is ordinarily a cofactor of factor VIII, is not present. Fortuitously, after the completion of the survey of the Trace database, a draft assembly based on the same database was posted. The draft assembly allowed many of the identified Trace fragments to be linked into longer sequences that fully support the conclusion that lampreys have a simpler clotting scheme compared with other vertebrates. The data are also consistent with the hypothesis that a whole-genome duplication or other large scale block duplication occurred after the divergence of jawless fish from other vertebrates and allowed the simultaneous appearance of a second set of two functionally paired proteins in the vertebrate clotting scheme.     

Cancer chemotherapy and anticoagulant prophylaxis

The modern pathobiochemical explanation of the old clinical finding, i.e. that the occurrence of the thromboembolic complications in cancer patients is significantly higher, starts to be clarified on the basis of recent knowledge regarding the role of cancer procoagulant, the expressed tissue factor and the changes in the clotting and fibrinolytic systems. Furthermore, the presently used chemotherapeutic agents have activating effects of the coagulation system as well. The details of these phenomena, the frequently used drugs and their pathobiochemical effects are detailed in this publication. Finally, it gives an outlook regarding the new adjuvant, beneficial effects of the direct anticoagulants in malignancies.