T2DM患者血浆vWF：Ag检测及意义

目的探讨血管性血友病因子抗原（vWF：Ag）在2型糖尿病（T2DM）发生、发展中的作用。方法将172例T2DM患者据UAER水平分为尿白蛋白正常组、微量白蛋白尿组、临床白蛋白尿组;另选60例健康人为正常组。检测各组血浆vWF：Ag水平并分析其与糖化血红蛋白（HbA1c）、血小板计数（PC）、平均血小板体积（MPV）和血小板分布宽度（PDW）等指标的相关性。结果与正常组比较,微量白蛋白尿组、临床白蛋白尿组vWF：Ag、UAER、HbA1c和PC、MPV和PDW均显著升高（P均〈0.01）。多元逐步回归分析示血浆vWF：Ag水平与UAER、HbA1c、PC、MPV和PDW呈显著正相关（r分别为0.804、0.664、0.858、0.784、0.820,P均〈0.01）。结论早期检测vWF：Ag对糖尿病肾病早期诊断、血管内皮细胞损伤程度、糖尿病血糖控制情况、血栓形成倾向有重要意义。     

血浆血管性血友病因子水平与冠状动脉病变的关系

目的:测定血浆血管性血友病因子(vWF)浓度,探讨血浆vWF水平与冠状动脉病变之间的关系。方法:根据冠状动脉造影结果选择冠心病患者78例,分为单支病变组、双支病变组、多支病变组,测定其血浆vWF水平,并与冠状动脉病变积分作相关分析。同时选非冠心病患者29例作为正常对照组。结果:冠心病组血浆vWF水平较正常对照组血浆vWF水平明显升高,(181.24±26.56)%∶(157.11±26.63)%,P<0.01;多支病变组较单支病变组、双支病变组的血浆vWF水平明显升高,(195.52±26.57)%∶(165.24±26.90)%、(180.54±18.58)%,P分别<0.01、<0.05;双支病变组较单支病变组的血浆vWF水平也明显升高(P<0.05),对照组与单支病变组的血浆vWF水平无差异。血浆vWF水平与冠状动脉病变积分呈正相关(r=0.702,P<0.01)。结论:血浆vWF水平可较好反映冠心病患者血管内皮功能损伤程度和冠状动脉病变范围。     

不同分期2型糖尿病患者血浆vWF水平变化及与血液流变学指标的相关性

目的 探讨血浆血管性血友病因子(vWF)水平变化在2型糖尿病(T2DM)疾病进展中的作用.方法 对143例不同分期 T2DM患者(观察组)和30例健康查体者血浆vWF水平进行了测定,并分析其与血液流变学指标的相关性.结果 观察组各期血浆vWF水平及血液流变学指标均显著高于对照组,且随病程进展呈进行性升高;血浆vWF水平与血液流变学各指标均呈显著正相关.结论 血浆vWF水平升高可能在T2DM病情进展中起重要作用;监测血浆vWF水平和血液流变学指标对于T2DM慢性微血管病变、血管动脉粥样硬化的预防及早期诊治具有重要意义.     

vWF、vWF—CP在2型糖尿病伴肾病患者中的水平及其影响因素

目的 分析血管性血友病因子（vWF）和血管性血友病因子裂解蛋白酶（vWF-CP）在2型糖尿病伴肾损害患者中的水平,并对其影响因素进行分析。方法将81例2型糖尿病伴肾病患者分为大量、正常、微量白蛋白尿组,并择42例健康对照作为对照组。采用ELISA法检测vWF,R—CBA法检测vWF—CP,并分析其与肾功能的相关性。结果对照组、正常白蛋白尿组、微量白蛋白尿组、大量白蛋白尿组中,血浆vWF水平呈阶梯样升高,血浆vWF—CP水平呈阶梯样下降（P均〈0．05）。Pearson相关分析表明,vwF与尿蛋白排泄率呈正相关,vWF—CP与尿蛋白排泄率、血尿酸、vWF呈负相关（P〈0．01）。结论血浆vWF、vWF-CP水平与糖尿病肾脏损害相关联,并且随着糖尿病肾脏损害的进展呈阶梯样改变。     

急性冠脉综合征并糖尿病患者凝血-纤溶功能的研究

目的研究冠心病、糖尿病患者的血栓形成异常状态,探讨凝血、纤溶机能及血管内皮功能变化在冠心病、糖尿病的发生发展中的作用。方法检测25例急性冠脉综合征患者(A组)、15例Ⅱ型糖尿病患者(B组)和15例急性冠脉综合征合并Ⅱ型糖尿病患者(C组)的血浆凝血因子Ⅶ (Coagulation factor Ⅶ, FⅦ)、von Willebrand因子(vWF)水平及纤溶酶原激活物抑制因子1(Plasminogen Activator Inhibitor-1, PAI-1),与对照组20例健康人比较,A、C组中15例还检测了常规治疗10～14 d后的各指标水平。结果 A组的三项指标皆较对照组明显升高;C组FⅦ水平高于B、D组,PAI-1水平与B组相似,明显高于对照组,vWF水平低于A、B组,差别无显著性;B组FⅦ水平近似于对照组,PAI-1和vWF水平升高。在B、C组中,FⅦ与血清总胆固醇水平呈正相关(r=0.63,P＜0.001),与高密度脂蛋白水平呈负相关(r=-0.52,P＜0.001)。在正常对照组中,vWF与FⅦ水平呈负相关(r=-0.56,P＜0.05)。A、C两组中15例患者在经治疗后vWF水平显著降低而FⅦ水平略升高(P＜0.05),PAI-1活性无变化。结论急性冠脉综合征及糖尿病患者具有血栓前状态的特征性改变,血浆FⅦ、PAI-1及vWF水平可能是急性冠脉综合征的预测因子,并与Ⅱ型糖尿病有一定相关性,常规治疗可改善内皮功能,不影响FⅦ及PAT-1水平。     

急性冠状综合征并糖尿病患者凝血—纤溶功能的研究

目的　研究冠心病、糖尿病患者的血栓形成异常状态 ,探讨凝血、纤溶机能及血管内皮功能变化在冠心病、糖尿病的发生发展中的作用。方法　检测 2 5例急性冠脉综合征患者 (A组 )、15例Ⅱ型糖尿病患者 (B组 )和 15例急性冠脉综合征合并Ⅱ型糖尿病患者 (C组 )的血浆凝血因子Ⅶ(CoagulationfactorⅦ ,FⅦ )、vonWillebrand因子 (vWF)水平及纤溶酶原激活物抑制因子 1(PlasminogenActivatorInhibitor 1,PAI 1) ,与对照组 2 0例健康人比较 ,A、C组中 15例还检测了常规治疗 10～ 14d后的各指标水平。结果　A组的三项指标皆较对照组明显升高 ;C组FⅦ水平高于B、D组 ,PAI 1水平与B组相似 ,明显高于对照组 ,vWF水平低于A、B组 ,差别无显著性 ;B组FⅦ水平近似于对照组 ,PAI 1和vWF水平升高。在B、C组中 ,FⅦ与血清总胆固醇水平呈正相关 (r =0 6 3 ,P <0 0 0 1) ,与高密度脂蛋白水平呈负相关 (r=- 0 5 2 ,P <0 0 0 1)。在正常对照组中 ,vWF与FⅦ水平呈负相关 (r =- 0 5 6 ,P <0 0 5 )。A、C两组中 15例患者在经治疗后vWF水平显著降低而FⅦ水平略升高 (P <0 0 5 ) ,PAI 1活性无变化。结论　急性冠脉综合征及糖尿病患者具有血栓前状态的特征性改变 ,血浆FⅦ、PAI 1及vWF水平可能是急性冠脉综合征的预测因子 ,并与     

vWF、Ⅷ因子水平变化与易栓症患者静脉血栓发生率的关系

目的探讨血管性血友病因子(vWF)、Ⅷ因子在获得性易栓症患者血浆中的水平及其临床意义。方法78例获得性易栓症患者中男45例,女33例,其中发生静脉血栓的15例;60例健康体检者作为对照组,男34例,女26例。对患者的vWF、Ⅷ因子水平进行对比分析,及时发现血栓前状态,初步探讨vWF、Ⅷ因子水平的改变在获得性易栓症患者发生静脉血栓中的价值。结果发生静脉血栓的获得性易栓症患者血浆vWF、Ⅷ因子水平明显高于未发生静脉血栓者(P0.05),获得性易栓症患者血浆vWF、Ⅷ因子水平明显高于正常对照组(P0.05)。结论获得性易栓症患者vWF、Ⅷ因子水平的改变,对患者发生静脉血栓有一定临床价值。     

2型糖尿病微量白蛋白尿患者血浆血小板活化因子的检测及其临床意义

目的研究2型糖尿病微量白蛋白尿患者血浆血小板活化因子(PAF)的水平及其与尿白蛋白排泄率(UAER)的相互关系.方法采用生物学方法和放免法分别测定30例健康人(正常对照组)、30例2型糖尿病正常白蛋白尿患者、28例2型糖尿病微量白蛋白尿患者血浆PAF和UAER水平.结果 (1)正常对照组与正常白蛋白尿组相比UAER、血浆PAF均无显著性差异(P>0.05);(2)在排除代谢因素影响后,2型糖尿病组中微量白蛋白尿组与正常白蛋白尿组相比血浆PAF有非常显著性差异(P<0.01);(3)UAER与PAF正相关,相关系数0.68,尤其在微量白蛋白尿组,相关系数达0.74.结论血浆PAF增高可能参与了2型糖尿病微量白蛋白尿的发生、发展过程,它的检测可作为早期糖尿病肾病的诊断、治疗、预后观察的一个临床指标.     

检测2型糖尿病患者血浆同型半胱氨酸水平的临床意义探讨

目的 探讨2型糖尿病(DM)患者血浆同型半胱氨酸(HCY)水平及意义。方法 用化学发光法对55例肾功正常的2型DM患者[DM组,其中无肾病38例、早期糖尿病肾病17例(DN)例]及51例健康人(对照组)的血浆HCY水平进行测定比较,同时分析血浆HCY与DM患者年龄、病程、血压、血浆叶酸(Fol)、维生素B12、总胆固醇(CH)、肌酐(SCr)及尿白蛋白排泄率(UAER)之间的相关性。结果 DM组血浆HCY水平均较对照组明显升高(P<0.01),合并早期肾病者血浆HCY水平较无肾病者明显升高(P<0.05);DM患者血浆HCY水平与UAER及SCr呈显著正相关(P<0.05),与其他因素间无明显相关性。结论 糖尿病患者尤其是合并肾脏损害者血浆HCY明显升高,高HCY血症可能是DN发生发展的危险因素之一。     

脑梗死患者血浆EDRF、vWF、TNF含量变化探讨

目的观察脑梗死患者内皮细胞舒张因子(EDRF),血管性假血友病因子(vWF)及肿瘤坏死因子(TNF)血浆中的含量。方法测定42例急性期脑梗死患者,38例恢复期脑梗死患者及40例正常人血浆E-DRFv、WF、TNF含量,并分析其相互关系。结果(1)急性期脑梗死患者vWF、TNF较对照组明显升高(P<0.01),EDRF明显降低(P<0.01)。(2)大梗死组与小梗死组相比较,vWF、TNF水平升高和EDRF水平下降均有显著差异(P<0.01)。(3)急性期脑梗死患者vWF升高与TNF呈正相关(r=0.72、P<0.01),vWF升高与E-DRF呈负相关(r=-0.74,P<0.01)。(4)恢复期脑梗死患者vWF、TNF及EDRF与对照组比较,无显著差异(P>0.05)。结论急性脑梗死患者存在内皮细胞损伤和功能障碍。     

Clinical significance of von Willebrand factor in patients with adult dermatomyositis

Because the clinical significance of von Willebrand factor (vWF), a marker of endothelial injury, has not been well studied in adult patients with dermatomyositis (DM), we evaluated whether plasma vWF levels are useful as an index of disease activity in these patients. We measured plasma vWF antigen levels in 11 patients with active adult DM, 13 patients with inactive DM, and 18 healthy subjects using an enzyme-linked immunosorbent assay. The association of vWF level with clinical condition and muscle-derived enzyme leakage among DM patients was examined using analysis of covariance and logistic regression analysis. Furthermore, we studied the effects of treatment on the vWF antigen level. The mean vWF antigen level was significantly higher in active DM patients than in inactive DM patients and healthy subjects. Higher vWF levels were associated with clinical symptoms, such as general fatigue, fever, and muscle weakness. They were also associated with the levels of aspartate aminotransferase, alanine aminotransferase, and aldolase, but not with those of lactate dehydrogenase and creatine kinase (CK). vWF antigen was correlated with muscle enzymes except for CK. The plasma vWF levels in six patients with active DM significantly decreased after successful corticosteroid treatment. Plasma vWF level may be considered a useful marker of disease activity in adult DM patients.     

高血压病患者血浆血管性假血友病因子及D-聚合体水平的变化

目的　探讨高血压病和缺血性脑卒中发生发展过程中凝血因子 相关抗原血管性假血友病因子 (v WF)及D-聚合体 (D- D)水平的变化及临床意义。方法　用酶联免疫双抗体夹心法分别测定 2 0 0例高血压病患者 (其中包括76例急性缺血性脑卒中患者 )和 76例健康对照者的血浆 D- D及 v WF水平 ,比较高血压 2级、3级及合并急性缺血性脑卒中时的 D- D及 v WF的变化。结果　高血压病 3级血浆 v WF显著高于高血压 2级及正常对照组 (P<0 .0 1) ;高血压 2级也高于正常对照组 (P<0 .0 5 ) ;缺血性脑卒中急性期治疗前后二者比较差异显著 (P<0 .0 0 1) ,各级高血压病 D- D变化无差异。结论　随着高血压病的进展 ,血浆中 v WF水平随之升高 ,急性缺血性脑卒中发生时达到高水平 ,经过治疗后 v WF水平下降     

Elevation of plasma von Willebrand factor and tumor necrosis factor-a in obese subjects and their reduction by the low molecular weight heparin tinzaparin.

AIM: Increased plasma-soluble von Willebrand factor (vWF) level, a marker of vascular endothelial cell dysfunction, is a predictor of atherosclerotic cardiovascular disease. We compared associations between vWF level and markers of inflammation as well as the effects of LMWH in obese as compared to healthy human subjects. METHODS: Plasma samples were obtained from healthy volunteers (n=32) and obese subjects (n=12) before and after administration of a single subcutaneous dose of tinzaparin, given at 75 IU/kg once a day, a deep vein thrombosis prophylaxis dose. Plasma samples were analyzed for vWF and tumor necrosis factor-alfa (TNF-alfa) using specific and sensitive ELISA. RESULTS: Obese subjects showed relatively higher plasma levels of TNF-alfa compared with normal-weight subjects. Regression analysis showed that plasma vWF levels to be directly associated with the presence of higher plasma levels of TNF-alfa in these obese subjects. Tinzaparin significantly reduced elevated plasma levels of both vWF and TNF-a levels (P<0.01). CONCLUSIONS: Plasma values of vWF and TNF-alfa are higher in obese than in normal-weight individuals. Treatment with tinzaparin lowers plasma levels of TNF-alfa in both obese and normal-weight subjects. The levels of vWF were higher in obese subjects than in normal-weight ones, which might be due to the higher levels of circulating TNF-alfa. Tinzaparin reduced vWF levels in these obese subjects.     

充血性心力衰竭患者口服ACEIs后血浆ox-LDL、vWF及TAC改变的临床意义

目的本研究观察了67例充血性心力衰竭（CHF）患者口服培哚普利和依那普利后血浆氧化型低密度脂蛋白（ox-LDL）、血管性假血友病因子（vWF）及总抗氧化能力（TAC）的改变,探讨血管紧张素转换酶抑制剂（ACEIs）对体内氧化状态和血管内皮功能的影响。方法67例CHF患者随机给予依那普利或培哚普利治疗8周后,观察血浆ox-LDL、vWF及TAC水平的改变。35例健康志愿者作为正常对照组。血浆vWF和ox-LDL采用酶标法测定,血浆TAC水平采用分光光度计测定。结果两组CHF患者基础血浆ox-LDL、vWF水平高于健康对照组（P<0.01）,血浆TAC水平低于正常对照组（P<0.01）;服药4周后,依那普利组和培哚普利组血浆ox-LDL、vWF水平下降（P<0.05）,8周后进一步下降（P<0.01）;而血浆TAC水平在4周时升高（P<0.05）,8周时进一步升高（P<0.01）。结论ACEIs如依那普利和培哚普利能提高CHF患者的抗氧化能力,改善血管内皮功能以及降低血栓形成倾向,从而对阻断CHF的恶性循环起到有益作用。     

原发性高血压病人血管性假血友病因子及超敏C反应蛋白的检测意义

目的原发性高血压病人与正常人群对照,探讨血管性假血友病因子（vWF）及超敏C反应蛋白（hs-CRP）检测值的临床意义。方法选45例原发性高血压病人及45名体检正常者,空腹取肘静脉血,采用酶联免疫吸附双抗体夹心法（ELISA）测定血浆vWF含量;采用免疫比浊法测定hs-CRP含量。结果原发性高血压病人vWF及hs-CRP含量显著高于正常人群组（P〈0.01）;原发性高血压组中,随着年龄增大,vWF含量增高;70岁以上年龄段男性较女性升高尤明显（P〈0.01）;各年龄段按高血压分级vWF含量有统计学意义。结论vWF是血管内皮受损的标志物,hs-CRP是组织损伤、炎症反应的标志,原发性高血压病人存在内皮细胞受损及炎症反应,内皮细胞受损及炎症反应程度与年龄、病情呈正相关。原发性高血压发病机制可能与vWF及hs-CRP升高相关。     

Re-elevation of high-sensitivity C-reactive protein but not the von Willebrand Factor after withdrawing atorvastatin therapy in patients with unstable angina undergoing coronary artery stenting

Statins are known to reduce high-sensitivity C-reactive protein (hs-CRP) concentrations and improve endothelial function. However, whether statin withdrawal causes re-elevated concentrations of hs-CRP and von Willebrand Factor (vWF) (a marker of endothelial damage) remains unknown. We hypothesized that the concentrations of hs-CRP and vWF are substantially increased in patients with unstable angina pectoris (UAP) and noticeably decreased following coronary stenting along with atorvastatin therapy. However, re-elevations of these biomarker concentrations occurred once again after withdrawing atorvastatin therapy. We serially examined the plasma concentrations of hs-CRP and vWF in 51 patients with UAP before (day 0) and after (days 21, 90, 180, 270) performing coronary artery stenting. The concentrations of these 2 biomarkers were also measured in 30 healthy control subjects. Patients were treated with atorvastatin (40 mg/day orally) for 180 days, after which the therapy was withdrawn. The hs-CRP and vWF concentrations were significantly higher in the patients than in the healthy control subjects before the procedure (both P values < 0.001). The hs-CRP concentration decreased significantly on day 21 (P < 0.001), and further to a substantially lower level on day 180 (P < 0.0001). However, the hs-CRP level significantly increased again on day 270, as compared with that on day 180 (P < 0.001). The vWF plasma concentration decreased gradually to a significantly lower level on day 180. The concentration of this biomarker did not differ between days 180 and 270. In conclusion, although hs-CRP concentrations decreased markedly following combined stenting and atorvastatin therapy, re-elevation after atorvastatin therapy was withdrawn in UAP patients undergoing coronary stenting was not observed. Conversely, restoration of endothelial function was slow and persistent in these patients.     

Angiotensin-converting enzyme activity is involved in the mechanism of increased endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes mellitus.

The renin-angiotensin system plays an important role in the elevation of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in hypertensive patients, so the present study was designed to examine whether angiotensin-converting enzyme (ACE) activity is also involved in the mechanism of ADMA elevation in type 2 diabetes mellitus (NIDDM). A crossover study was performed to determine if ACE inhibition with perindopril (4 mg/day) for 4 weeks decreases serum ADMA concentration and plasma von Willebrand factor (vWF) level (a marker of endothelial injury) in 11 patients with NIDDM. None of the patients was treated with insulin or oral hypoglycemic drugs, and none had major diabetic complications. Before the protocol began, serum ADMA and plasma vWF were significantly higher in the 11 NIDDM patients, when compared with 8 control subjects without diabetes. Perindopril did not affect blood pressure or glucose metabolism, but did significantly decrease serum ADMA and plasma vWF. These results suggest that endothelial injury associated with ADMA elevation may be present even in patients with non-complicated NIDDM, and that increased activity of ACE may be involved in such endothelial dysfunction.     

系统性红斑狼疮患者血管内皮细胞损伤标志物检测及其临床意义

目的探讨血管内皮细胞损伤与系统性红斑狼疮(SLE)疾病活动、肾脏损伤的关系。方法应用酶联免疫吸附试验(ELISA)检测31例SLE患者和10例健康对照者血浆可溶性血栓调节蛋白(sTM)、血管假性血友病因子(vWF)水平。结果SLE组血浆sTM、vWF水平明显高于对照组;SLE组血浆sTM、vWF水平均与疾病活动指数(SLEDAI)呈显著正相关,与24小时尿蛋白定量呈正相关。结论血管内皮损伤可能在SLE发病机制中起重要作用,血浆sTM、vWF水平可作为判断SLE疾病活动性及肾脏损伤程度的指标。     

Von Willebrand factor (vWF) antigen levels and function in healthy Thais

Type I von Willebrand disease (vWD) is very common in caucasians. Its genetic basis is possibly heterogenous, lying both within and out of the vWF gene locus. We sought to investigate vWF levels in the Thai population, to compare with those of western countries. The vWF antigen and activity were measured using ELISA and Collagen Binding Assay (CBA), respectively, in 311 healthy Thai volunteers. The mean age was 32.3, ranging from 18 to 75 years. Fifty-four percent were female. Low vWF antigen and activity (below 50 U/dl) were found in 3.5% and 10.2%, respectively. Around 75% and 20% of these cases had O and A blood groups, respectively. Three (0.96%) had definitely low levels of vWF (vWF antigen level below 35 U/dl), suggesting the diagnosis of vWD. Similar to previous studies, vWF levels were lowest in subjects with group O blood. We found that subjects with blood group A had higher vWF levels than group O subjects, but significantly lower vWF levels than those with group B. The average ratio between the vWF activity and antigen was 0.96, ranging from 0.66 to 1.66. These ratios were inversely correlated with age (p=0.047), suggesting a decline in vWF activity per vWF protein with advancing age. Low levels of vWF are common in healthy Thais. Clinicians should be aware of vWD in bleeding patients and beware low levels of vWF in therapeutic plasma products, especially from blood groups O and A.     

缬沙坦对伴有高血压病的代谢综合征患者血管性假血友病因子的影响

目的 观察伴有高血压病的代谢综合征（metabolic syndrome,MS）患者血浆血管性假血友病因子（von Willebrand factor,vWF）水平及应用缬沙坦后vWF的变化。方法 测定22例伴有高血压病的MS患者服用缬沙坦80 mg/d4周前后及29例健康体检者血浆vWF含量。结果 伴高血压病的MS患者血浆vWF显著高于健康对照者［(176±24)% vs (130±26)%,P<0.01］;vWF含量与收缩压（SBP）［r＝0.60,P<0.01］、舒张压（DBP）［r＝0.57,P<0.01］、平均动脉压（MAP）［r＝0.61,P<0.01］、体质量指数（BMI）［r＝0.53,P<0.01］、三酰甘油（TG）［r=0.36,P<0.05］、总胆固醇（TC）［r=0.49,P<0.01］、空腹血糖（FBG）［r＝0.45,P<0.01］呈正相关;缬沙坦治疗4周后,伴高血压病的MS患者血浆vWF水平较治疗前显著降低［(160±15)% vs (176±24)%,P<0.01］。结论 伴高血压病的MS患者血浆vWF水平较健康人明显增高;予缬沙坦治疗后,在有效降低血压的同时,可短期内降低vWF水平,改善血管内皮功能。