纤溶活性在2型糖尿病冠心病的研究

目的观察2型糖尿病（DM）无血管病变组（A组）43例与DM并冠心病组（B组）41例及对照组（C组）40例的纤溶活性。方法测定124例患者的组织纤溶酶原激活物（tPA）、纤溶酶原激活抑制物-1（PAI-1），并对A组追踪观察上述指标2年。结果①PAI-1在A、B组都高于C组；B组高于A组；②tPA在A、B组都低于C组；B组低于A组，上述差异都有统计学意义（P〈0．05或P〈0．01）。结论①DM发生临床血管病变前即有纤溶异常，发生血管病变则改变更显著。②上述指标可作为反映DM血管病变的预测及监测指标。     

ET/NO、t-PA/PAI-1及TXA2/PGI2与糖尿病肾病的关系

糖尿病肾病（DN）患者肾脏微血管病变的发生发展与血管内皮细胞损伤、血小板活化、纤溶活性降低密切相关。血管内皮功能受损时，对血管内皮细胞合成分泌的多种血管活性肽，如内皮素（ET）、一氧化氮（NO）、组织型纤溶酶原激活物（t—PA）、纤溶酶原激活物抑制剂（PAI）-1有明显的影响，而纤溶活性降低与PA活性降低及PAI增加有关。现就ET／NO、t—PA／PAI-1及血栓素（TXA2）／前列环素（PGI2）与DN的关系综述如下。     

2型糖尿病患者凝血、抗凝及纤溶功能的变化

目的：探讨2型糖尿病（DM）患者凝血、抗凝及纤溶活性的改变及其临床意义。方法：应用酶联免疫吸附双抗体夹心法及发色底物法测定2型DM患者血中凝血酶原片段1＋2（F1＋2）、可溶性纤维蛋白单体复合物（SFMC）、抗凝血酶（AT）、组织型纤溶酶原激活剂（t-PA）和纤溶酶原激活物抑制剂-1（PAI-1）活性。纤维蛋白原（Fbg）测定为Claus法。结果：①2型DM患者的Fbg、F1＋2、SFMC、及PAI-1较正常对照组有显著性增高,AT和t-PA表现为显著性降低（P〈0.05）;②DM有并发症组与DM无并发症组相比较,上述凝血、抗凝及纤溶各指标间亦差异有统计学意义（P〈0.05）;③各指标改变的幅度随病变的程度增加而加重。结论：2型DM患者的凝血活性亢进、抗凝和纤溶活性降低,导致凝血-纤溶功能紊乱,表现为血液高凝状态,当DM患者有并发症存在时更为明显。为临床上对糖尿病患者使用抗凝剂及抗血小板药物治疗提供了理论依据。     

2型糖尿病纤溶系统变化与胰岛素抵抗的关系

目的探讨2型糖尿病患者纤溶活性变化与胰岛素抵抗之间的关系。方法采用酶联免疫吸附法测定63例2型糖尿病患者（包括无血管并发症组30例和有血管并发症组33例）和25例正常对照者血浆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）含量，结合临床资料分析其变化趋势及影响因素。结果2型糖尿病患者血浆t-PA含量明显降低（P〈0．01），而PAI-1含量明显升高（P〈0．01），合并血管病变者，此变化更为显著（均P〈0．001）。多元逐步回归分析显示，HOMA模型胰岛素抵抗指数（HOMA—IR）是PAI-1升高的独立危险因素。结论2型糖尿病患者纤溶活性降低，胰岛素抵抗在降低其纤溶活性，并发血管病变中起了重要作用。     

156例2型糖尿病PAI-1基因启动子区4G/5G多态性及其相关因素分析

检测156例2型糖尿病（T2DM）和60名正常人血浆纤溶酶原激活物抑制物1（PAI-1）启动子4G／5G多态性，与有关临床指标作相关分析，结果提示PAI-1基因4G／SG多态性可能与T2DM发生冠心病相关。     

PAI-1基因与血栓性疾病

纤溶功能下降是多种血栓性疾病的重要发病机制之一，纤溶酶原激活剂抑制物（plasminogen activator inhibitor PAI）约占纤溶系统抑制物活性的60％，PAI-1是其中最重要的成分。自二十世纪八十年代首次发现PAI-1以来，人们对其血浆水平与多种疾病的关系进行了多方面的研究，普遍认为血浆PAI-1水平升高使纤溶功能下降与多种血栓性疾病有显著的关系。二十世纪九十年代，人们对PAI-1基因及其多态性给予更大的关注，本文将对PAI-1基因多态性对血浆PAI-1水平的影响及与冠心病、脑血管病、外周血管血栓的关系进行综述。     

以纤溶酶原激活物抑制剂1为靶标的心血管疾病治疗研究进展

<正>纤溶系统的主要功能是溶解血管中沉积的纤维蛋白,从而促进血栓溶解。纤溶酶原激活物具有启动和活化纤溶系统的作用,而纤溶酶原激活物抑制剂1(PAI-1)则抑制纤溶反应的发生,组织型纤溶酶原激活剂(t-PA)与PAI-1的动态平衡对纤溶系统的稳态具有重要作用。近年,PAI-1在心血     

2型糖尿病并大血管病变患者血浆纤溶酶原激活物抑制剂1及凝血酶激活的纤溶抑制物水平变化及意义

目的:探讨2型糖尿病(DM)并大血管病变患者血液中纤溶酶原激活物抑制剂1(PAI-1)、血浆组织型纤溶酶原激活物(t-PA)、D-二聚体(D-D)以及血浆凝血酶激活的纤溶抑制物(TAFI)水平的变化及临床意义。方法:分别应用ELISA及乳胶免疫分析测定DM患者血浆PAI-1、t-PA、TAFI、D-D活性;并与糖尿病无大血管并发症组和健康对照组比较。结果:DM组PAI-1、t-PA、D-D和TAFI含量分别为(48.36±7.92)ng/mL、(12.52±3.17)ng/mL、(0.75±0.58)mg/L和60.82%±14.71%,与健康对照组相比有显著差异(P<0.01);其中糖尿病大血管病变组PAI-1、t-PA及D-D水平与糖尿病无大血管病变组有显著差异(P<0.01)。结论:糖尿病患者血液中PAI-1、t-PA、D-D、TAFI水平与血管损伤和功能变化的进程有显著相关性,联合检测上述指标对糖尿病及其并发症的诊断、治疗和病情观察有重要的临床意义。     

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.     

纤溶活性与2型糖尿病及其大血管病变

组织型纤溶酶原激活剂(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)是纤溶系统的主要调控因子.2型糖尿病患者高血糖、高胰岛素血症、脂代谢紊乱、炎症反应、肥胖等多种因素可引起血浆t-PA水平降低、PAI-1水平升高.纤溶活性的降低参与了大血管病变的发生、发展.提高纤溶活性的综合治疗将对防治糖尿病大血管并发症起一定作用.     

通络方剂对糖尿病大鼠PAI-1及血流变的作用

目的观察通络方剂(Tongluo Recipe,TLR)对糖尿病(Diabetes Mellitus,DM)大鼠PAI-1及血流变的作用,并探讨其可能机制。方法雄性SD大鼠腹腔注射链脲佐菌素(Streptozocin,STZ,60 mg/kg),1型糖尿病成模后,随机分为糖尿病组(DM),高剂量通络方剂组(HT,1 g.kg-1.d-1),低剂量通络方剂组(LT,0.5 g.kg-1.d-1),并设鼠龄、体重相匹配的正常对照组(NC),每组8只。12 w后ELISA法测定血浆纤溶酶原激活物抑制剂-1(Plasminogen activator inhibitor-1,PAI-1)含量,同时测定红细胞变形指数(EDI)和红细胞聚集指数(ECI)等血流变指标。结果NC组PAI-1含量(1.99±0.51)明显低于其他各组(P<0.01),DM组的PAI-1含量(11.36±0.60)高于HT组(4.25±0.73)及LT组(7.74±0.82)(P<0.05),HT组PAI-1含量低于LT组(P<0.05)。NC组、DM组EDI低于HT组及LT组(P<0.05),ECI高于HT及LT组。结论TLR可能通过改善血管内皮功能,抑制糖尿病大鼠PAI-1的生成,减少微血管血栓形成,对糖尿病大鼠血管病变具有保护作用。     

The effects of rosiglitazone treatment on the fibrinolytic system in patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.     

Impact of diabetes-associated lipoproteins on generation of fibrinolytic regulators from vascular endothelial cells.

Increased thrombotic tendency and decreased fibrinolytic activity have been frequently found in patients with diabetes mellitus (DM). Previous studies by our group indicated that nonenzymatically glycated low density lipoprotein (LDL) increased plasminogen activator inhibitor-1 (PAI-1) production and decreased the generation of tissue plasminogen activator (tPA) from cultured human umbilical vein endothelial cells (HUVEC). The present study demonstrates that plasma levels of PAI-1 or PAI-1/tPA were significantly increased in patients with type 1 (n = 10) and type 2 DM (n = 14) compared with those in healthy controls (n = 10; P < 0.05 or 0.01). LDL from patients with type 1 or type 2 DM, and very low density lipoprotein (VLDL) from patients with type 2 DM induced significantly greater increases in the release of PAI-1 and more profound reduction in tPA generation from HUVEC compared with corresponding lipoproteins from healthy controls (P < 0.05 or 0.01). HDL from diabetic patients did not significantly alter the generation of PAI-1 or tPA from endothelial cells (EC) compared with HDL from controls. Comparable effects of lipoproteins from DM patients on the generation of PAI-1 and tPA were found in human coronary artery EC. LDL and VLDL from patients with type 2 DM enhanced the activation of PAI-1 promoter (-1528/+55)/luciferase reporter gene transiently transfected in HUVEC (P < 0.01). The results of the present study suggest that LDL and VLDL from patients with DM reduce the generation of tPA and increase PAI-1 production through the activation of the PAI-1 promoter in vascular EC.     

不同血糖状态下血清超敏C反应蛋白、纤溶酶原激活物抑制物-1水平的变化及与胰岛素抵抗的关系

目的检测不同血糖状态人群空腹血清超敏C反应蛋白（hs—CRP）、纤溶酶原激活物抑制物-1（PAI-1）水平,探讨hs—CRP、PAI-1与胰岛素抵抗之间的关系。方法选取健康对照组、糖耐量减低组、2型糖尿病组受试者各30例,测定受试者空腹血清hs—CRP、PAI-1、血脂、空腹胰岛素等项目,应用稳态模型评估法评价胰岛素抵抗。结果2型糖尿病组、糖耐量减低组、对照组依次比较,hs—CRP、PAI-1、胰岛素抵抗指数均有显著升高（P均〈0．05）;多元逐步回归分析显示体重指数、hs—CRP、PAI-1是影响胰岛素抵抗的重要危险因素。结论2型糖尿病人群、糖耐量减低人群存在明显的胰岛素抵抗,hs—CRP、PAI-1、BMI是加重胰岛素抵抗的危险因素;糖调节受损时期即可能存在慢性炎症反应,并出现大血管病变的一些病理生理改变。     

初诊2型糖尿病患者血清PAI-1、NO、3-NT与FMD的相关性研究

目的探讨初诊2型糖尿病患者血清纤溶酶原激活物抑制剂1(PAI-1)、一氧化氮(NO)和3-硝基酪氨酸(3-NT)水平的变化及其与肱动脉血流介导的内皮依赖性血管舒张功能(FMD)之间的关系,探讨血管内皮功能障碍的危险及保护因素。方法选取2012年7月—2013年3月收治的初诊T2DM患者144例,其中从未接受过降糖治疗的初诊的T2DM患者作为观察组,选取72名性别及年龄相匹配的健康体检者作为对照组,用ELISA法检测血清PAI-1、NO和3-NT,采用高分辨超声技术分别检测FMD。结果①两组对象在年龄、性别、BMI方面差异无统计学意义(P>0.05)。观察组MAP、TC、TG、FPG、HbA1c、HOMA-IR高于对照组,差异有统计学意义(P<0.05);观察组HOMA-β低于对照组,差异有统计学意义(P<0.05)。②与对照组比较,观察组PAI-1、3-NT明显增高,NO、FMD明显降低,差异有统计学意义(P<0.05)。③相关分析显示,观察组血清PAI-1、3-NT与FMD呈负相关;而NO与FMD呈正相关。④多元回归分析显示,NO是血管内皮功能的保护因素,而PAI-1、MAP是血管内皮功能的危险因素。结论初诊T2DM患者存在明显的纤溶异常、氧化硝化反应和血管内皮依赖性血管舒张功能障碍,在糖尿病早期治疗中关注改善纤溶异常和减轻氧化硝化反应在一定程度上可保护血管内皮功能,延缓糖尿病血管并发症的发生发展。     

PAI-1、Fg与2型糖尿病患者颈动脉硬化的研究

目的分析循环血中纤溶酶原激活物抑制物-1(PAI-1)、纤维蛋白原(Fg)在2型糖尿病人群及非糖尿病人群中的差异。探讨PAI-1、Fg与2型糖尿病患者颈动脉硬化的相关性。方法对158例心内科住院患者及42名健康体检者检查血糖、空腹胰岛素、血脂、尿酸(UA)、血常规、凝血三项、PAI-1、Fg,测量血压、腰围(WC)、身高和体重,并计算体重指数(BMI);通过颈动脉超声测量颈动脉内膜中层厚度(IMT)。分析PAI-1、Fg与2型糖尿病患者IMT的相关性。结果与正常对照组人群相比,2型糖尿病组患者PAI-1、Fg水平明显升高(P<0.05),2型糖尿病合并颈动脉硬化组患者PAI-1、Fg水平均显著高于2型糖尿病无颈动脉硬化组患者及正常对照组人群(P<0.05)。多元回归分析显示,2型糖尿病患者的血浆PAI-1、Fg水平与颈动脉IMT独立相关,提示体内PAI-1、Fg水平的高低与2型糖尿病患者颈动脉硬化程度密切相关。结论 PAI-1、Fg水平升高可能是2型糖尿病合并大血管病变的危险因素。     

Correlation of conjunctival microangiopathy with retinopathy in type-2 diabetes mellitus (T2DM) patients

We hypothesized that T2DM vasculopathy can be revealed and quantified in the bulbar conjunctiva prior to its pathologic presentation in the retina. Using computer-assisted intravital microscopy (CAIM), an objective, non-invasive approach can provide a viable complement to retinal fundus photography to possibly screen patients for early signs of real-time, in vivo T2DM vasculopathy. Fundus photography was utilized to determine the retinopathy level (RL) in T2DM patients with non-proliferative diabetic retinopathy (NPDR) and control subjects. CAIM was used to quantify microangiopathy in the bulbar conjunctiva in the same patients, and reported on a severity index (SI). The average RL for the T2DM patients in this study is 19.68 ± 9.91, which differs from control subjects (RL = 10 ± 0.0; p < 0.05). A significant difference in vasculopathy was observed in the conjunctival microcirculation in the same patients (SI = 5.81 ± 1.30) when compared with control subjects (SI = 1.33 ± 1.58; p < 0.05). The results provide evidence that significant vasculopathy had developed in the microcirculation in the bulbar conjunctiva, though diabetic retinopathy had not developed significantly in the same patients - indicative of the presence of a time window for early intervention of T2DM before non-proliferative retinopathy develops, and the real-time availability of the conjunctival microvasculature as an in vivo platform to monitor disease progression.     

2型糖尿病血清脂联素与心血管相关标志物相关性的研究

目的检测老年糖尿病(DM)患者血清脂联素(APN)与3个心血管相关标志物水平并探讨二者之间的相关关系。方法将70例老年受试者分为3组:正常对照组、老年DM未合并大血管病变组(DM1)和老年DM合并大血管病变组(DM2),检测血清APN与心血管相关标志物-血浆C反应蛋白(c-reactive protein,CRP)、Ⅰ型血浆纤溶酶原活化抑制剂(plasminogen activator inhibitor type-1,PAI-1)和血清基质金属蛋白酶-9(matrx metalloproteinase-9,MMP-9)的水平变化。结果从正常对照组、DM1到DM2组血清APN水平依次下降,各组间差别均具有显著意义(均P<0.01)从正常对照组、DM1到DM2组,CRP、PAI-1、MMP-9的水平逐渐升高,CRP、PAI-1升高在各组间均具有显著性(均P<0.05),MMP-9在DM2组开始出现显著升高(P<0.01),DM1组较正常对照组升高没有显著意义。APN水平与CRP、PAI-1、腰围、BMI、WHR及FBG、2h PBG、HbA1C、TG呈显著负相关。多元逐步回归分析显示APN与CRP(r2=0.18)、PAI-1(r2=0.16)、WHR(r2=0.21)及HbA1C(r2=0.19)具有高度的相关性(均P<0.05)结论APN可能是老年DM动脉粥样硬化发生发展中的保护因素。     

Low micromolar concentrations of copper augment the impairment of endothelium-dependent relaxation of aortae from diabetic rabbits

Both diabetes mellitus (DM) and elevated plasma copper concentrations are risk factors for cardiovascular disease (CVD). DM is associated with impaired endothelial nitric oxide (NO) and with excess superoxide (O2*-) formation. Copper is also elevated in DM and is also associated with the generation of O2*-. To explore possible interactions between DM and copper, the effect of exogenous copper (CuCl2) on endothelium-dependent relaxation and cyclic guanosine monophosphate (GMP) formation was investigated in aortae from diabetic rabbits. Rabbits were rendered diabetic by intravenous injection of alloxan. Six months after induction of DM, the aortae were excised, cut into rings, and mounted in an organ bath for isometric measurement of acetylcholine (Ach)-evoked relaxation in rings precontracted with phenylephrine (PE). In parallel studies, cyclic (c)GMP formation by aortic rings following stimulation with Ach, calcium ionophore A23187 (A23187) and sodium nitroprusside (SNP) was assessed using radioimmunoassay. The effect of copper on these parameters was then studied using the same methods. Ach-evoked relaxation and Ach- and A23187-evoked cGMP formation were significantly impaired in aortae from diabetic rabbits compared to controls, effects that were reversed with superoxide dismutase (SOD) and catalase (CAT). In contrast, there were no significant differences in SNP-stimulated relaxation or cGMP formation in aortae from diabetic rabbits compared to controls. Copper (1 to 10 micromol/L) promoted a further significant inhibition of Ach-stimulated relaxation in aortae from diabetic but not control rabbits. This reduction by copper was again reversed by SOD and CAT. We conclude that copper augments the reduction of NO bioavailability, which is already impaired in aortae from diabetic rabbits due to excess production of O2*- and H2O2. These results indicate that patients with DM may be susceptible to copper-mediated vasculopathy at much lower concentrations than those that promote vasculopathy in nondiabetic patients.     

糖尿病大鼠PAI-1 mRNA的表达与心肌微血管改变的相关性研究

目的通过研究老龄和青年糖尿病（DM）大鼠心肌微血管数目与心肌组织PAI-1mRNA表达的改变,探讨高血糖和增龄对心肌微血管数目及心肌组织PAI—1mRNA表达的影响。方法老龄和青年SD大鼠分别随机分为DM组和对照组,STZ液腹腔注射建立DM大鼠模型,喂养8周后,处死大鼠,取部分左心室组织进行免疫组化;剩余部分留做心肌组织PAI-1mRNA检测。采用EnVision免疫组化法,CD34抗体检测心肌微血管内皮细胞特异性抗原CD34。利用医学图像分析软件计数心肌微血管数目。实时荧光定量PCR法检测各组心肌组织PAI—1mRNA的表达。结果各年龄段大鼠,DM组心肌微血管数目显著低于同龄段对照组（P〈0．01）,DM组心肌组织PAI-1mRNA的表达与同龄对照组相比则显著增多（P〈0．01）;老龄DM组心肌微血管数目明显低于青年DM组及青年对照组（P〈0．01）,老龄对照组心肌微血管数目与青年对照组无明显统计学差异（P〉0．05）,而老龄DM组心肌组织PAI-1mRNA表达显著高于青年DM组及青年对照组（P〈0．01）;并且老龄对照组心肌PAI-1mRNA的表达也高于青年对照组（P〈0．05）。结论增龄对DM大鼠心肌微血管数目有影响,而对非DM大鼠无明显影响。增龄使大鼠心肌组织PAI-1mRNA表达增强。各年龄段DM大鼠心肌微血管数目减少,心肌组织PAI-1mRNA表达增强。