血管紧张素-(1-7)对氧化低密度脂蛋白诱导人血管内皮细胞纤溶功能异常的调节

目的 探讨血管紧张素-(1-7)[Ang-(1-7)]对氧化低密度脂蛋白(ox-LDL)诱导血管内皮细胞分泌组织型纤溶酶原激活物(t-PA)及其抑制物-1(PAI-1)的影响。方法 用酶消化法收集并培养人脐静脉内皮细胞(HUVECs),分别以不同终浓度的Ang-(1-7)(10、100、1000nmol/L)和ox-LDL[25、50、100mg/L(蛋白质含量)]进行单独或联合刺激,并以A-779(终浓度为100nmol/L)进行干预,孵育24h。以ELISA方法检测培养基上清液中t-PA和PAI-1蛋白含量,RT-PCR法检测PAI-1和t-PAmRNA的表达。结果 ox-LDL使PAI-1的分泌量显著增加,t-PA分泌显著降低,PAI-1mRNA表达升高,t-PAmRNA表达降低(P<0.001~0.05),并呈剂量依赖性;Ang-(1-7)使PAI-1分泌量及PAI-1mRNA表达显著降低,亦呈剂量依赖性(P<0.01~0.05),而对t-PA分泌及t-PAmRNA表达无影响;在混合刺激组中,与ox-LDL组比较,Ang-(1-7)使PAI-1及PAI-1mRNA表达降低、t-PA及t-PAmRNA表达升高(P<0.01~0.05),但PAI-1及PAI-1mRNA表达仍高于对照组,t-PA及t-PAmRNA表达仍低于对照组(P<0.05)。加入A-779后,Ang-(1-7)的作用消失。结论 Ang-(1-7)对氧化低密度脂蛋白诱导的血管内皮细胞纤溶异常具有显著的调节作用,此作用是通过特异性受体介导的。     

TNF-α对人脐静脉内皮细胞t-pA、pAI-1表达的研究

目的：观察肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）对人脐静脉内皮细胞（HUVECs）组织型纤溶酶原激活物（tissue plasminogen activitor,t-PA）及其抑制剂-1（plasminogen activitor inhibitor-1,PAI-1）表达的影响。方法：原代分离HUVECs细胞并进行传代培养,分别以6个TNF-α浓度组（0、1、10、20、50、100 ng·m L-1）处理不同时间（0、1、3、6、12、24 h）,酶联免疫吸附分析（ELISA）法测定t-PA、PAI-1抗原的表达;逆转-聚合酶链反应（RTPCR）检测t-PA、PAI-1基因的表达。结果：TNF-α促进PAI-1抗原的表达,并呈剂量和时间依赖关系,在TNF-α10 ng·m L-1作用6 h时最明显（P〈0.01）;TNF-α促进PAI-1 mRNA的表达,并呈剂量和时间依赖关系,在TNF-α10 ng·m L-1作用3 h时已非常明显（P〈0.01）,6 h时达到高峰（P〈0.01）;而TNF-α对HUVECs表达t-PA抗原、mRNA无明显影响。结论：炎症因子TNF-α可能通过上调PAI-1表达而诱发血栓相关疾病。     

急性脑梗死患者纤溶系统与血管内皮功能的关系

目的探讨脑梗死患者血管内皮功能与组织型纤溶酶原激活物抑制剂-1(PAI-1)的关系。方法纳入108例脑梗死患者(脑梗死组)和110例正常人(健康对照组),采用高分辨超声技术检测血流介导的肱动脉舒张功能(FMD)和硝酸甘油介导的肱动脉舒张功能(NTG),并测定血浆纤溶酶原激活物(t-PA)和PAI-1水平。结果(1)脑梗死组FMD较健康对照组明显减弱[(9±5)%vs(11±4)%,P<0.01)],而2组NTG差异无统计学意义[(17±8)%vs(20±8)%,P>0.05];(2)脑梗死组血浆PAI-1水平显著高于健康对照组[(63±10)ng/mlvs(44±8)ng/ml,P<0.01],而血浆t-PA水平显著低于健康对照组[(12±4)ng/mlvs(13±3)ng/ml,P<0.05];(3)脑梗死组血PAI-1与血管内皮功能呈显著负相关(r=-0.65,P<0.01)。结论(1)脑梗死患者血浆PAI-1活性与血管内皮功能呈负相关,PAI-1活性增高导致血浆纤溶活性降低,可能是血管内皮功能异常引起脑梗死的中间环节;(2)血管内皮功能异常可改变纤溶活性,是脑梗死发生的危险因素。     

高静水压培养对人脐静脉内皮细胞t-PA和PAI-1的影响

目的探讨高静水压培养对人脐静脉内皮细胞（HUVECs）t—PA和PAI-1的影响及其可能的作用机制。方法选用第4～6代HUVECs，接种于24孔培养板中。依培养压力分为3组：大气压组（0mmHg），中压组（90mmHg）和高压组（180mmHg），每组18份标本。在同一压力组，根据不同药物干预又分为3个亚组：对照组（Ctrl组），双丁酰环磷腺苷组（DBA组，10μmoL／L）和硝普钠组（NP组，10^-4moL／L），每组6份标本。采用ELISA法测定上清液t-PA和PAI-1的抗原浓度，并用细胞内总蛋白进行标化，同时测定细胞内Ca^2＋浓度。结果与大气压组的对照组比较，中压和高压组t-PA浓度均显著降低（P〈0.01），PAI-1浓度显著增高（P〈0.01），t-PA／PAI-1比值显著降低（P〈0.01），[Ca^2＋]i也显著增高（P〈0.01）。cGMP诱导剂NP显著降低三个压力组的PAI-1浓度（P〈0.01）和增高t—PA／PAI-1比值（P〈0.05），cAMP的同功异构体DBA显著升高三个压力组的PAI-1浓度（P〈0．01，P〈0．05）。DBA和NP对t-PA浓度没有显著影响（P〉0.05）。结论高静水压可损害内皮细胞的抗纤溶功能。第二信使cAMP、cGMP和细胞内钙离子在此可能起调节作用。     

组织型纤溶酶原激活剂及其抑制物的变化与冠心病的关系

目的：观察冠心病患者纤溶活性的变化及其在冠心病发病中的作用，探讨其临床意义。方法：用酶联免疫双抗夹心(ELISA)法测定58例冠心病患者血浆中组织型纤溶酶原激活剂(t—PA)及纤溶酶原激活抑制物-1(PAI-1)抗原含量，反映纤溶-抗纤溶活性的变化，并对冠心病患者组与对照组纤溶指标进行不同性别间的比较。结果：急性心肌梗死、不稳定心绞痛患者PM-1的含量、PAI-1／t—PA比值明显高于对照组，且急性心肌梗死患者PM-1的含量较不稳定心绞痛患者显著为高。但t—PA在急性心肌梗死、不稳定心绞痛患者均无显著降低。患者组及对照组不同性别间纤溶及抗纤溶水平均未见有显著差异。结论：血栓性疾病与纤溶系统的异常有密切关系。纤溶系统活性的变化及纤溶-抗纤溶的平衡失调在缺血性心脏病的发生、发展中起着重要作用。     

组织型纤溶酶原激活物及其抑制物与静脉血栓栓塞症的关系

目的探讨组织型纤溶酶原激活物(t-PA)及其抑制物-1(PAI-1)血浆水平与静脉血栓栓塞症的关系。方法 87例肺动脉血栓栓塞(PTE)患者,根据是否合并深静脉血栓形成(DVT)分为2组:合并DVT患者52例,未合并DVT患者35例,同期入选性别、年龄匹配对照者80例。酶联免疫吸附试验测定血浆PAI-1和t-PA水平,聚合酶链反应-限制性片段长度多态性法检测PAI-1基因型。结果未合并DVT组t-PA明显降低,PAI-1明显升高,与合并DVT组、对照组比较差别有统计学意义(P<0.05),而合并DVT组与对照组比较差别无统计学意义(P>0.05)。在3组中,无论何种基因型,未合并DVT组的PAI-1血浆水平均最高。在4G/4G基因型和4G/5G基因型中,未合并DVT组与对照组和合并DVT组比较差别均有统计学意义(P<0.05)。结论未合并DVT的PTE患者存在明显的低纤溶状态。     

辛伐他汀调控RhoA对血管平滑肌细胞增殖与迁移及纤溶活性的影响

目的:探讨不同浓度辛伐他汀调控小G蛋白RhoA及下游激酶ROCK信号对人主动脉血管平滑肌细胞(HAVSMCs)增殖和迁移,以及组织纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)表达的影响及作用机制。方法:应用不同浓度Simvastatin(0.1μmol/L、1μmol/L、10μmol/L)处理HAVSMCs,CCK-8法和"划痕实验"分别检查细胞增殖和迁移能力,RT-qPCR检测RhoA mRNA及下游ROCK mRNA表达,应用RT-qPCR和ELISA检测纤溶活性相关t-PA/PAI-1mRNA及蛋白活性变化。结果:辛伐他汀呈浓度依赖性显著抑制HUASMCs的增殖和迁移能力。辛伐他汀能够显著抑制RhoA/ROCK信号途径,诱导PAI-1 mRNA表达下调从而抑制蛋白分泌表达,同时上调t-PA mRNA表达从而增加蛋白分泌表达,以10μmol/L辛伐他汀组处理24 h效果最为显著。结论:辛伐他汀呈浓度时间依赖性抑制RhoA/ROCK信号途径,并且上调t PA以及下调PAI-1基因转录及蛋白表达,从而促进纤溶,抑制细胞增殖和迁移。     

Gene expression of fibrinolytic factors urokinase plasminogen activator and plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage with disc displacement

Background The urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1(PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling.Methods Disc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques.Results The expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks.Conclusions The expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.     

PDGF对大鼠肾小球系膜细胞表达纤维连接蛋白和PAI-1的影响

目的：探讨血小板源性生长因子fPDGF）对体外培养的大鼠肾小球系膜细胞表达纤维连接蛋白（VN）和纤溶酶原激活物抑制剂-1（PAI-1）的影响。方法：分别以0、5、10ng／rnl的PDGF—BB刺激体外培养的大鼠肾小球系膜细胞12、24、48h．以ELISA法检测培养上清中FN水平，发色底物显色法检测PAI-1的活性；以0、5、10ng／ml的PDGF—BB刺激大鼠系膜细胞24h和10ng／ml PDGF-BB分别作用0、12、24、48h。RT-PCR方法检测系膜细胞PAI-1 mRNA的表达。结果：PDGF-BB在10ng／ml以内随浓度增加可促进大鼠肾小球系膜细胞PAI-1 mRNA和FN表达．在48h内其表达呈时间依赖性。而PAI-1活性在24h时表达最高，以后逐渐下降、结论：PDGF-BB可上调FN和PAI-1及其mRNA表达．提示PDGF可能通过促进细胞外基质合成并抑制其降解而导致肾小球细胞外基质的积聚。     

Relationship between tissue type plasminogen activator and coronary vulnerable plaque in patients with acute coronary syndrome: virtual histological study

Background The association between vulnerability of plaque assessed with intravascular ultrasound （IVUS） and plasma levels of fibrinolytic biomarkers was determined in patients with acute coronary syndrome （ACS）. However, few data are available on the relationship between the levels of tissue type plasminogen activator （t-PA） and virtual histological intravascular ultrasound （VH-IVUS） signs of plaque instability. Methods Eighty-nine patients with ACS were enrolled in the study. Blood was collected to measure t-PA levels by liquid phase bead flow cytometry. Eighty-nine nonbifurcate lesions （identified by coronary angiography and ECG） were investigated using IVUS before catheterization. IVUS radiofrequency data obtained with a 20 MHz catheter were analyzed with IVUS virtual histological software. The areas of plaque and media were calculated and lesions were classified into two groups： VH-IVUS derived thin cap fibroatheroma （VH-TCFA） and non-VH-TCFA plaque. Results Plasma t-PA level in the patients with TCFA was significantly lower than that with non-TCFA （（1489 ± 715） pg/ml vs （2163 ± 1004） pg/ml）. Decreased plasma levels of t-PA were associated with plaque vulnerability. Plasma levels of t-PA correlated negatively with plaque plus media and necrotic core in plaque in patients with ACS. Conclusions t-PA is an independent risk factor and a powerful predictor of vulnerable plaques. Decreased levels of t-PA may reflect instability of atherosclerotic plaques and might therefore serve as noninvasive determinants of those at high risk for consequent adverse events.     

老年抑郁症患者治疗前后血浆脑源性神经营养因子和组织纤维蛋白溶酶原激活物水平的变化

目的 探讨老年抑郁症患者治疗前后血浆脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)和组织纤维蛋白溶酶原激活物(tissue-type plasminogen activator,tPA)水平的变化,为老年抑郁症的诊断和治疗提供生物学指标.方法 用酶联免疫吸附法(ELISA)测定28例老年抑郁症患者冶疗前后和30例正常对照组血浆中BDNF和tPA的水平,使用汉密尔顿抑郁量表(Hamilton Depression Rating Scale,HDRS)评分反映抑郁严重程度.结果 与对照组[(958.83±150.20)pg/ml]比较,治疗前老年抑郁症患者血浆BDNF水平[(864.23±198.41)pg/ml]明显降低(P<0.05),治疗后血浆BDNF水平[(929.99±150.90)pg/ml]有升高趋势;患者组治疗前[(13.33±5.35)ng/ml]、治疗后[(11.83±5.02)ng/ml]及正常对照组[(12.53±5.35)ng/ml]间tPA水平差异无显著性(P>0.05);治疗前血浆BDNF和tPA之间相关无显著性.结论 BDNF可以作为老年抑郁症的一个生物学标记,tPA与BDNF之间可能存在复杂的中间调节过程.     

Activation of peroxisome proliferator-activated receptor α in human endothelial cells increases plasminogen activator inhibitor type-1 expression

Objective To investigate the effect of peroxisome proliferator-activated receptors(PPARs) activators on plasminogen activator inhibitor 1(PAI-1) expression in human umbilical vein endothelial cells and elucidate a possible mechanism.Methods Human umbilical vein endothelial cells(HUVECs) were obtained from normal fetus,and cultured conventionally.Then the HUVEC were exposed to fatty acids and prostaglandin J2 in varying concentrations with fresh media.RT-PCR and ELISA were used to determine the expression of PPAR and PAI-1 in HUVECs.Transient co-transfection of PAI-1 promoter and PPARα gene or PPARγ gene to ECV304 was performed.Results PPARα,PPARγ and PPARγ mNRA in HUVECs were detected by RT-PCR.Treatment of HUVECs with PPARα and PPARγ activators-linolenic acid,linoleic acid,oleic acid and prostaglandin J2,but not with stearic acid could augment PAI-1 mRNA expression and protein secretion in a concentrationdependent manner.Proportional induction of PAI-1 promoter activity was observed through increasing amounts of PPARαDNA in HUVECs throgh a transient gene transfection assay,although the mRNA expression of the 3 subtypes of PPAR with their activators were not changes compared with controls.Conclusions HUVECs express PPARs,PPARs activators may increase PAI-1 expression in endothelial cells(EC).Although PPARs expresslon was not enhanced after being stimulated by their activators in EC,the functionally active PPARαis probably involved in regulating PAI-1 expression in EC.     

辛伐他汀对不稳定型心绞痛患者纤溶活性的影响

目的:通过辛伐他汀对不稳定型心绞痛患者血浆组织型纤溶酶原激活物t-PA与纤溶酶原激活抑制剂-1(PAI-1)的影响,来探讨其对不稳定型心绞痛患者纤溶活性的影响。方法:61例不稳定性心绞痛患者随机分为2组:常规治疗组30例,辛伐他汀治疗组31例,比较其在治疗前、后t-PA、PAI-1的活性水平的变化。结果:辛伐他汀治疗后PAI-1降低,差异有显著性;t-PA活性呈上升趋势,但无统计学意义(P>0.05);结论:辛伐他汀可明显改善不稳定型心绞痛患者血浆纤溶活性。     

乳腺癌患者血浆尿激酶型纤溶酶原激活系统的变化及其意义

目的 :观察乳腺癌患者血浆尿激酶型纤溶酶原激活物 (u -PA)及其特异性受体 (u -PAR)和纤溶酶原激活物抑制物 - 1 (PAI- 1 )含量的变化及其与肿瘤转移和预后的关系。方法 :用ELISA法测定 2 2例乳腺癌患者和 2 1例正常人血浆中u -PA、u -PAR和PAI- 1含量。结果 :乳腺癌患者的血浆u -PA、u -PAR和PAI - 1含量均显著升高 (P <0 .0 5～ 0 .0 1 ) ;中、晚期组u -PA显著高于早期组 (P <0 .0 5 ) ,已转移组u -PA、u -PAR和PAI- 1较未转移组显著升高 (P <0 .0 5～ 0 .0 1 )。结论 :乳腺癌患者血浆中u -PA、u -PAR和PAI - 1含量不同程度升高 ,并与肿瘤转移和预后相关     

醛固酮对系膜细胞合成纤溶酶原激活剂抑制物-1的影响

目的 探讨醛固酮及阻断其受体后对系膜细胞生成纤溶酶原激活剂抑制物1（PAI-1）的影响。方法 醛固酮单独刺激大鼠系膜细胞24h以及采用螺内酯阻断后,用RT-PCR观察系膜细胞PA1-1mRNA的变化;用Western印迹方法检测细胞上清液中的PA1-1;采用ELISA方法测定细胞上清液中转化生长因子p1（TGF-β1）的含量;采用激光共聚焦检测系膜细胞内的活性氧（ROS）水平。观察不同浓度及不同作用时间的醛固酮刺激系膜细胞对PA1-1mRNA的影响。结果 醛固酮使系膜细胞PA1-1mRNA及蛋白表达明显升高,同时升高了TGF-β1的表达和细胞内的ROS水平。醛固酮使PA1-1mRNA表达呈剂量依赖性增加。100nmol／L醛固酮刺激系膜细胞4h后PA1-1mRNA表达才明显增加。加用螺内酯后使升高的PA1-1、TGF-β1表达以及细胞内ROS恢复到正常水平。结论醛固酮能独立促进大鼠系膜细胞分泌PA1-1的增加,同时醛固酮使TGF-β1表达以及细胞内ROS水平升高,而这些都是通过盐皮质激素受体介导的。     

冠脉介入治疗后止凝血功能的改变及其与PAI基因多态性的关系

目的：探讨经皮冠状动脉介入术( PCI)后止凝血功能变化与纤溶酶原激活剂抑制物-1 (PAI-1) 基因启动子区-675 4G/5G 多态性的关系,为临床PCI后预测血栓形成提供依据。方法：86例行PCI的冠心病患者分别于术前、术后即刻、术后24 h肘静脉采血,检测血浆中血管性血友病因子( vWF) 、PAI-1、FⅦc活性及血小板α颗粒膜蛋白-140（GMP-140 ）、D-二聚体(D-D)含量;应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测基因型及不同基因型患者PCI前、后止凝血功能指标。结果：PAI-1 基因型频数分布为4 G/4 G 型48 例（56%）,4 G/5 G30 例（35%）,5 G/5 G 型 8 例（9%）。4 G 和5 G 等位基因频率分别为73%和27%。3组基因型患者术前各项指标比较差异无显著性（P>0.05）。具有PAI-1 4G/4G 基因型患者血浆vWF、PAI-1、FⅦc活性及GMP-140、D-D含量在术后即刻高于术前( P< 0.01);术后24 h PAI-1活性高于术前(P< 0.01),但vWF、FⅦc活性及GMP-140、D-D含量有所下降,与术前比较差异无显著性（P>0.05）。具有4G/5G基因型及5G/5G基因型的两组患者术后即刻各项指标较术前明显增高( P< 0.01);术后24 h较术前有增高趋势,但差异均无显著性（P>0.05）。4 G/4 G 型患者术后即刻及术后24 h PAI-1活性较另两组基因型患者增高更显著( P< 0.01);其他指标有增高趋势,但差异无显著性(P>0.05)。结论：具有PAI-1 4 G/4G 基因型患者在PCI后较4 G/5 G型及5 G/5 G 型患者存在明显的纤维蛋白溶解功能的改变,提示PAI-1 4G/4G基因可能是PCI后急性和亚急性冠状动脉血栓形成的危险基因型。     

预处理对大鼠缺血冠脉等组织t—PA,PAI—1基因表达的影响

采用Northern印迹杂交、斑点杂交、原位杂交技术和发包庇物显色测定方法研究急性心肌缺血大鼠冠脉等组织t－PA、PAI－1基因表达和t－PA活性变化、缺血预处理对这些改变的影响。结果表明：（1）缺血组冠脉等组织t－PA活性明显低于对照组，预处理组高于缺血组，3组组间比较均P＜0．01。（2）Northern和斑点杂交显示急性心肌梗塞时t－PA、PAI－1mRNA表达均增高，分别为对照大鼠的1．2和4．6倍，预处理组PAI－1mRNA表达明显降低，t－PAmRNA表达与缺血组近似。（3）心肌组织原位杂交检测到t－PA、PAI－1mRNA主要分布在冠脉血管，尤其集中于内皮细胞。上述结果提示，心肌缺血损伤时t－PA、PAI－1mRNA均异常表达，其中PAI－1的高表达是心肌缺血时纤溶活性降低的主要原因，预处理恢复组织中t－PA活性与PAI－1mRNA表达减少密切相关。以上结果为预处理保护机制研究提供了新的资料。     

Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 m RNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol

目的　研究米非司酮配伍米索前列醇药物流产后蜕膜纤溶酶原激活剂及其抑制物 (PA、PAI)变化 ,探讨药物流产后异常子宫出血的机理。方法　 4 5例早孕受试者随机平均分成 3组 :正常蜕膜组、米非司酮组和米非司酮米索前列醇药物流产组。应用逆转录 -聚合酶链反应 (RT PCR)技术、发色底物法和酶联免疫吸附试验 (ELISA)法观察 3组蜕膜组织型纤溶酶原激活剂 (tPA)和I型纤溶酶原激活剂抑制物 (PAI 1)mRNA及蛋白表达水平。结果　米非司酮米索组和米非司酮组tPA活性分别为 4 6 91± 2 0 74IU/mgprotein和 64 2 5± 35 81IU/mgprotein ,低于正常蜕膜组 (P <0 0 5) ;tPAmRNA水平以米非司酮米索组最高 ( 1 4 3± 0 39,P <0 0 5) ,而另 2组之间无差异 (P >0 0 5) ;PAI 1mRNA和蛋白水平 3组间均无差异 (P >0 0 5)。结论　米非司酮和米索前列醇经转录后途径降低人早孕子宫蜕膜tPA活性 ,可影响蜕膜剥落、血管再生、内膜复修而致药物流产后子宫出血时间过长。     

Activity of Ginkgo biloba extract and quercetin on thrombomodulin expression and tissue-type plasminogen activator secretion by human umbilical vein endothelial cells

INTRODUCTION Ginkgo biloba extract (GBE) has been used as a ommonly prescribed drug in traditional Chinese edicine for several thousand years. GBE is still sed in clinics in Europe to alleviate symptoms ssociated with blood circulation disorder. It has be…     

Rhein inhibits transforming growth factor β1 induced plasminogen activator inhibitor-1 in endothelial cells

Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mechanism of the protective action of rhein on endothelial cells. Methods A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFβ1 was determined by immunoprecipitation analysis and western blot. Results TGFβ1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFβ1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFβ1 in human endothelial cells. Conclusions Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.