Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells

We compared peritoneal dialysis effluents from 18 CAPD patientswho had not suffered from peritonitis during the last 6 months(group 1) with the effluents from five patients with acute peritonitis(group 2), measuring activation markers of coagulation and fibrinolysis.These markers included prothrombin fragment F1+2 (F1+2), thrombin-antithrombinIII complex (TAT), fibrin monomer (FM), and fibrin degradationproducts (FbDP). In the dialysate of group 1 we found remarkablyhigh levels of F1+2, TAT and FM concomitant with a high concentrationof FbDP, indicating a high rate of intraperitoneal fibrin turnover.The balance between peritoneal generation and degradation offibrin was disturbed in untreated patients of group 2, who hadsignificantly higher levels of coagulation markers and a higherratio between FM and FbDP. Seven days after treatment with intraperitonealadministration of antibiotics and heparin, F1+2, TAT, FM andFbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritonealfibrin turnover we investigated the expression of tissue-typeplasminogen activator (t-PA), urokinase-type plasminogen activator(u-PA), plasminogen activator inhibitor type-1 (PAI-1), andtissue factor in cultured human peritoneal MC under basal conditionsand after exposure to tumour necrosis factor (TNF) interleukin-1(IL-1), or bacterial lipopolysaccharide (LPS). The exposureof MC to TNF or to a lesser extent IL-1 or LPS reduced theirfibrinolytic activity by decreasing t-PA production and increasingPAI-1 synthesis. Furthermore the addition of TNF resulted inactivation of the coagulation cascade by the expression of tissuefactor. These in-vitro findings explain the imbalance betweenintraperitoneal coagulation and fibrinolysis during peritonitisof CAPD patients.     

In vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastograph technique

BACKGROUND: To investigate the in vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastograph (TEG) technique. METHODS: The blood samples, obtained from 14 healthy volunteers, were divided into two groups: propofol (n = 7) and intralipid (n = 7), and 360 microliters volumes of whole blood were incubated with 2 microliters of 1% propofol and with its solvent intralipid, respectively. The incubated sample was then used for TEG measurements. RESULTS: The maximum amplitude (MA), which reflects coagulability, in the intralipid group significantly increased by about 7% and 16% compared to the control and propofol groups, respectively (P < 0.05), whereas the MA in the propofol group did not change. The fibrinolytic rate (FR) in the propofol group significantly increased by about 170% and 210% compared to the control and intralipid groups, respectively (P < 0.05), whereas the FR in the intralipid group did not change. CONCLUSIONS: Propofol, per se, has at the concentration of 55.6 micrograms.ml-1 an in vitro accelerative effect on blood fibrinolysis detected by TEG.     

胃肠道恶性肿瘤t-PA、u-PA转录的临床研究

目的：研究胃肠道恶性肿瘤患者纤溶分子标志物血浆含量、mRNA水平的变化，初步探讨两者与肿瘤浸润、播散的关系及其临床检测意义。方法：采用逆转录、实时定量PCR技术检测23例胃癌、17例肠癌患者组织中组织型纤溶酶原激活剂(t—PA)、尿激酶型纤溶酶原激活剂(u—PA)mRNA水平；用ELISA法同步检测患者血浆纤溶分子标志物含量，包括t—PA、u—PA、尿激酶型纤溶酶原激活剂受体(u—PAR)、纤溶酶—抗纤溶酶复合物(PAP)等。结果：胃癌、肠癌组患者血浆u—PA、u—PAR、PAP蛋白含量均较正常对照明显升高，其中，有局部浸润、淋巴结转移、远处脏器转移者u一：PA升高更为显著；t—PA含量与正常对照无显著差异。u—PAmRNA在两种肿瘤细胞表达均显著增高，而t—PAmRNA则减少。结论：纤溶功能亢进是胃肠道恶性肿瘤细胞易播散、浸润的主要原因之一。t—PAmRNA水平的升高可能为组织分化较好的特征。     

氨甲环酸在开胸手术中的应用

目的评价氨甲环酸在开胸手术中的止血作用和对开胸手术围术期凝血纤溶功能的影响。方法选择因罹患肺或食管肿瘤的开胸手术患者40例,随机分为两组:氨甲环酸组(A组,n=20)在麻醉诱导后切皮前静脉滴注10mg/kg氨甲环酸,术中持续泵注1mg.kg-1.h-1至术毕;对照组(B组,n=20)持续泵注生理盐水。分别于术前,术中3h,术后第1天和第3天抽取中心静脉血检测血栓弹力图(TEG),凝血常规,包括凝血酶原时间(PT),部分活化凝血酶时间(APTT)和纤维蛋白原(Fib)含量,及血浆D-二聚体含量,并记录术中出血量和术后24h胸腔引流量。结果T组术中、术后CI均明显高于对照组,术后LY30显著低于对照组(P<0.05);T组术中和术后D-二聚体含量均明显低于C组(P<0.01);T组术中出血量和术后24h胸腔引流量明显少于C组(P<0.01)。结论氨甲环酸抑制了纤溶活性的增强,改善了开胸手术后早期的低凝状态,显著减少了开胸手术围术期的血液丢失。     

突发性耳聋患者血浆同型半胱氨酸血症与凝血-纤溶系统的变化

目的观察突发性耳聋(SSHL,突聋)患者血浆同型半胱氨酸(Hcy)与凝血-纤溶系统的变化关系,并探索其临床意义。方法收集突聋患者110例为病例组,另选110名性别、年龄和种族等与其相匹配的无突聋者作为对照组,采用荧光偏振免疫检测技术为基础的自动化免疫检测方法测定血浆同型半胱氨酸总量(t Hcy)。用发色底物法测定血浆中溶酶原激活剂抑剂因子-1(PAI-1)、组织型纤溶酶原激活剂(t-PA)活性;用PT-Der法测定纤维蛋白原的含量。结果突聋组血浆t Hcy水平(17.82±4.21)μmol/L显著高于对照组(13.71±3.59)μmol/L,P<0.01。病例组血浆PAI-1和t-PA活性分别为(23.4±2.5)U/mL和(0.8±0.2)U/mL;血浆纤维蛋白原(Fg)的平均浓度是(5.6±1.1)g/L。对照组血浆PAI-1和t-PA活性分别为(12.8±1.9)U/mL和(6.5±2.5)U/mL;血浆Fg的平均浓度是(2.8±0.6)g/L。结论在突聋患者中血浆t Hcy和凝血-纤溶系统的变化有密切相关性。血浆t Hcy、t-PA和Fg的检测有可能作为突聋患者治疗观察和愈后评价的参考指标。     

肺血栓栓塞症大鼠血浆尿激酶型纤溶酶原激活物及其受体的动态变化及其意义

目的观察大鼠肺血栓栓塞症(PTE)后不同时间血浆尿激酶型纤溶酶原激活物(uPA)和尿激酶型纤溶酶原激活物受体(uPAR)的动态变化,并探讨两者与血栓自溶率的相关性。方法经颈外静脉注入加热125I-标记纤维蛋白原自体血栓,复制大鼠PTE模型,随机分组如下:1)正常对照组;2)PTE组:又分为PTE 4 h组(PTE 4 h)、PTE 24 h组(PTE 24 h)、PTE 3 d组(PTE 3d)、PTE 5 d组(PTE 5 d),即分别在造模成功后观察4 h2、4 h3、d、5 d后处死小鼠,留取血浆标本测定uPA、uPAR的水平;留取左肺观察肺组织病理改变;留取心脏、肺脏、全血以计算血栓自溶率。结果血浆uPA、uPAR水平在PTE后4 h略有上升(P>0.05),PTE后24 h明显增加(P<0.05),3 d时最高(P<0.01),5 d时开始下降,但仍明显高于正常对照组(uPAP<0.05,uPARP<0.01);PTE后4 h组、24 h组、3 d组血浆uPA质量浓度与血栓自溶率正相关(4 hr=0.758,P<0.05;24 hr=0.764,P<0.05;3 dr=0.778,P<0.05),血浆uPAR质量浓度与血栓自溶率正相关(4 hr=0.701,P<0.05;24 hr=0.764,P<0.05;3 dr=0.777,P<0.05)。肺组织病理改变:PTE后4 h有少量继发血栓形成,血栓及血管壁内可见白细胞浸润;PTE后3 d、5 d见注入的血凝块明显溶解,代之以新形成的血栓。结论PTE后血浆uPA、uPAR水平增加,促进内源性纤维蛋白溶解。     

白藜芦醇苷对缺氧性肺动脉高压的作用

目的研究白藜芦醇苷对急性缺氧性肺动脉高压的血流动力学、纤溶系统及肺功能的作用.方法建立猪缺氧性肺动脉高压模型,观察静脉注射白藜芦醇苷前后的血液动力学、肺功能及血中纤溶指标的变化,并与对照组比较.结果用白藜芦醇苷后肺动脉压与用药前比较及与对照组比较均有显著下降(P＜0.01);心搏指数与对照组比较有所增加(P＜0.05);组织型纤溶酶原激活剂(t-PA)与用药前比较及与对照组比较有所增加(P＜0.05),血浆纤溶酶原激活剂抑制物的含量(PAI)与用药前比较及与对照组比较有所下降(P＜0.05).结论白藜芦醇苷可明显降低缺氧引起的肺动脉高压,增加心输出量,增强纤溶系统活性.     

Lesion-associated accumulation of uPAR/CD87- expressing infiltrating granulocytes, activated microglial cells/macrophages and upregulation by endothelial cells following TBI and FCI in humans

Urokinase-type plasminogen activator receptor (uPAR/CD87) together with its ligand, urokinase-type plasminogen activator (uPA), constitutes a proteolytic system associated with tissue remodelling and leucocyte infiltration. uPAR is a member of the glycosyl phosphatidyl inositol (GPI) anchored protein family. The functional role of uPAR comprises fibrinolysis by conversion of plasminogen to plasmin. In addition, uPAR promotes cell adhesion, migration, proliferation, re-organization of the actin cytoskeleton, and angiogenesis. Furthermore, uPAR is involved in prevention of scar formation and is chemoattractant to macrophages and leucocytes. In order to investigate the pathophysiological role of uPAR following human CNS injury we examined necrotic brain lesions resulting from traumatic brain injury (TBI; n = 28) and focal cerebral infarctions (FCI; n = 17) by immunohistochemistry. Numbers of uPAR+ cells and uPAR+ blood vessels were counted. Following brain damage, uPAR+ cells increased significantly within 12 h, reached a maximum after 3-4 days and remained elevated until later stages. uPAR was expressed by infiltrating granulocytes, activated microglia/macrophages and endothelial cells. Numbers of uPAR+ vessels increased in parallel subsiding earlier following FCI than post TBI. The restricted, lesion-associated accumulation of uPAR+ cells in the brain parenchyma and upregulated expression by endothelial cells suggests a crucial role for the influx of inflammatory cells and blood-brain barrier (BBB) disturbance. Through a failure in BBB function, uPAR participates in formation of brain oedema and thus contributes to secondary brain damage. In conclusion, the study defines the localization, kinetic course and cellular source of uPAR as a potential pharmacological target following human TBI and FCI.     

注射用苦碟子的抗凝与纤溶活性

目的观察注射用苦碟子抗凝和纤溶激活作用。方法采用测定全血凝块重量、凝血时间、优球蛋白溶解时间、血浆复钙凝血时间和凝血酶原时间的方法,观察注射用苦碟子对内源性和外源性凝血途径以及纤溶系统的影响。结果注射用苦碟子对内源性凝血途径具有较强的抑制作用,能够增加纤溶系统的活性;小鼠静脉给予注射用苦碟子6、12 mg.kg-1与对照组相比可显著降低全血凝块重量;大鼠静脉给予注射用苦碟子3.6、7.2 mg.kg-1可显著延长凝血时间,静脉给予注射用苦碟子1.8、3.6、7.2 mg.kg-1可显著缩短优球蛋白溶解时间;注射用苦碟子质量浓度为1.25、2.55、g.L-1时可显著延长血浆复钙凝血时间,离体凝血酶原时间与对照组相比无显著性差异。结论注射用苦碟子具有较强的抗凝血作用和纤溶活性。