尿激酶型纤溶酶原激活物受体在人脑胶质瘤中的表达及临床意义

应用流式细胞仪定量检测正常脑组织 (3例 )和胶质瘤 (32例 )标本中尿激酶型纤溶酶原激活物受体(u- PAR)含量 ,并探讨 u- PAR在人脑胶质瘤中的表达及其与临床各生物学参数的关系。结果显示 :u- PAR在人脑胶质瘤中的表达与病理分级呈显著正相关 (r=0 .83) ,而与病人性别、年龄、肿瘤部位、瘤体大小等因素无关。提示 u- PAR可作为判断人脑胶质瘤恶性程度和浸润潜能的一项参考指标。     

MMP-9和uPA在脑胶质瘤中的阳性表达及意义

目的 探讨脑胶质瘤组织中基质金属蛋白酶-9(MMP-9)、尿激酶型纤溶酶原激活剂(uPA)阳性表达及意义.方法 采用组织芯片技术和免疫组织化学S-P法检测50份脑胶质瘤组织、10份正常脑组织中MMP-9、uPA的阳性表达,并分析两者与患者临床病理特征的关系.结果 MMP-9和uPA在脑胶质瘤组织、正常脑组织中的阳性表达比较差异有统计学意义(P均＜0.05).MMP-9和uPA的阳性表达与脑胶质瘤患者的年龄、性别无明显相关性,但WHO分期Ⅲ、Ⅳ期明显高于Ⅰ、Ⅱ期(P均＜0.05);在脑胶质瘤组织中MMP-9的阳性表达与uPA的阳性表达呈正相关(r =0.456,P＜0.05).结论 MMP-9、uPA的阳性表达可能与脑胶质瘤的发生和恶性程度有关.     

t-PA、PAI活性测定在早期糖尿病肾病临床中的意义

目的 探讨2型糖尿病（T2DM）患者及糖尿病肾病（DN）患者中尿白蛋白排泄率（UAER）与血浆组织型纤溶酶原激活物（t-PA）、纤溶酶原激活物抑制物（PAI）活性的相关性。方法 选择60例T2DM病人，根据UAER分为单纯糖尿病（DMa）组、微量白蛋白尿组（DMb）和临床蛋白尿组（DMc）。此外，还选择了30例健康人作为对照组。采用发色底物显色法测定血浆t-PA和PAI的活性，并对其相关性进行统计分析。结果 （1）对照组、DMa组、DMb组和DMc组血浆卜PA活性递减，PAI的活性递增，各组比较有显著性差异（P〈0．01）。（2）t-PA与UAER呈负相关（r=0．615，P=0．000），PAI和UAER呈正相关（r=0．721，P=0．000）。结论 DN早期即有纤溶活性低下；t-PA和PAI可能作为DN肾脏损害程度的佐证，对指导临床用药以缓解或延迟DN的发生具有重要意义。     

肝细胞癌癌组织中uPA及其受体的表达及意义

目的 探讨肝细胞癌(HCC)的发生机制.方法 通过组织芯片及免疫组化法测定HCC癌组织中uPA及其受体(uPAR)的表达,并与肝硬化及正常肝组织比较. 结果 uPA在HCC、肝硬化、正常肝组织中的阳性表达率分别为74.0%、46.7%、20%,两两比较,P均＜0.05;随HCC分期进展及肿瘤直径增大,uPA表达阳性率逐渐升高.uPAR在HCC、肝硬化、正常肝组织中的阳性表达率分别为70.0%、63.3%、15.0%,与正常肝组织比较,P均＜0.05;uPAR阳性表达率随HCC分期进展表达逐渐上升,与肿瘤直径无密切关系.相关分析示,uPA和uPAR具有明显相关性.结论 HCC发生和发展是多因素共同作用的结果,其机制可能为uPA及uPAR高表达.     

宫颈鳞癌组织中uPA、uPAR的表达变化及意义

目的检测宫颈鳞癌组织中尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）的表达,并探讨其意义。方法采用免疫组织化学法分别检测正常宫颈组织、宫颈非典型增生组织及宫颈癌组织中的uPA、uPAR。结果uPA、uPAR的表达程度宫颈癌组织高于非典型增生宫颈组织,非典型增生宫颈组织高于正常宫颈组织（P均〈0．05）。宫颈癌组织中uPA、uPAR表达程度与临床分期和淋巴结转移有关（P均〈0．05）。结论宫颈癌组织中uPA、uPAR表达升高。其可能与宫颈癌的发生、发展、浸润、转移有关。     

t-PAA、PAIA活性测定在糖尿病肾病临床中的意义

目的：探讨糖尿病肾病（ＤＮ）临床中尿白蛋白排泄率（ＵＡＥＲ）与组织纤溶酶原激活物（ｔ－ＰＡＡ）、纤溶酶原激活物抑制物（ＰＡＩＡ）的相关性。地７１例糖尿病患者和３０例正常人的ＵＡＥＲ和ｔ－ＰＡＡ、ＰＡＩＡ进行测定,并对其相关性进行统计分析。结果：糖尿病组ｔ－ＰＡＡ随着ＵＡＥＲ的增高而降低,而ＰＡＩＡ则随着ＵＡＥＲ的增高而增高,糖尿病微量白蛋白尿组、临床蛋白尿组ｔ－ＰＡＡ与ＵＡＥＲ呈显著负相关（Ｐ〈０     

uPA及V-ATPase在肝细胞癌中的表达及意义

目的研究尿激酶型纤溶酶原激活物（uPA）和ATP动力型质子泵（V-ATPase）在肝癌细胞株的表达,及抑制V-ATPase与癌细胞抑制和凋亡的关系。方法用RT-PCR和Western blot检测稳定转染真核表达质粒pCMV-uPA-HA的HCC97L细胞及转染空载体pCMV-HA的HCC97L细胞中uPA和V-ATPase mRNA和蛋白的表达;在转染uPA的HCC97L细胞培养基中加入不同浓度的Bafilomycin A1,用流式细胞仪和CCK-8分别检测癌细胞凋亡及受抑制情况。结果将uPA转染入低转移潜能肝癌细胞株HCC97L后,uPA mRNA和蛋白表达强于转染空载体的HCC97L,V-ATPase mRNA和蛋白表达随着转染uPA而增强。在细胞培养基中加入Bafilomycin A1后细胞生长增殖受到抑制、凋亡增加,且抑制率和凋亡率均随Bafilomycin A1浓度的加大而增加。结论 V-ATPase mRNA和蛋白表达随癌细胞转移能力的提高而增强;Bafilomycin A1抑制V-ATPase,干扰癌细胞内H＋泵出,从而抑制癌细胞生长增殖、促进癌细胞凋亡。     

人股动脉粥样硬化斑块内尿激酶型纤溶酶原激活物受体的表达

目的选用正常乳内动脉作为对照,分析人股动脉粥样硬化斑块中尿激酶型纤溶酶原激活物受体（uPAR）在不同部位的表达差异。方法从2005年9月至2006年2月,收集我院血管外科行股动脉粥样硬化斑块剥脱术中获取的血管内膜或内-中膜标本20例,以及心脏外科行冠状动脉搭桥术中的正常乳内动脉标本16例。通过免疫组织化学染色等方法,观察uPAR在斑块中的表达情况;明确uPAR与内膜巨噬细胞、平滑肌细胞的关系;同时半定量检测斑块不同部位uPAR表达量的差异。结果uPAR在正常乳内动脉的内膜和中膜未见表达,但在粥样硬化斑块内膜uPAR的平均光密度值（A）为92±37,明显高于中膜（46±28,P〈0．05）;内膜uPAR的积分光密度值（IA）较中膜升高约7倍（P〈0．01）。内膜uPAR表达定位于巨噬细胞、泡沫细胞和平滑肌细胞处,以平滑肌细胞与uPAR分布最为一致。斑块肩部、脂质池、破裂及血栓形成部位的uPAR IA值分别为42131±31671、45747±19963和55344±23069,均明显高于相对正常部位（5072±2588,P〈0．05）,其中在斑块破裂处表达量最高。结论人股动脉粥样硬化斑块的肩部、脂质池和破裂处,uPAR表达明显升高,提示uPAR可能在斑块破裂中起着重要作用。     

纤溶指标检测在冠心病中的应用价值

凝血和纤溶系统的改变是导致冠心病(CHD)的重要因素之一,而纤溶系统的改变近来倍受关注。为此我们观察了124例CHD患者的纤溶指标变化及其相互关系,并探讨其临床应用价值。     

基层医院阿替普酶与尿激酶治疗急性ST段抬高型心肌梗死对比研究

目的：对比研究基层医院应用重组组织型纤溶酶原激活剂（rt—PA）阿替普酶与尿激酶（UK）治疗急性ST段抬高型心肌梗死（STEMI）的疗效及安全性。方法：资料完整的126例STEMI静脉溶栓患者,分为UK对照组（67例）和rt—PA治疗组（59例）,对溶栓再通情况和溶栓并发症进行评价,并择期行冠状动脉造影评价梗死相关动脉（IRA）心肌梗死溶栓（TIMI）血流,比较两组30d的主要不良心血管事件（MACE）发生率。结果：溶栓治疗后,与UK组比较,rt—PA组梗死相关血管再通率明显提高（56．7％％比81．4％）,左心衰竭（13．4％比5．1％）、心源性休克（7．5％比3．4％）、再缺血胸痛发生率（9．0％比3．4％）明显降低（P〈0．01）;皮肤穿刺部位轻度出血率升高（7．5％比27．1％,P〈0．05）;两组均未出现死亡病例,无严重出血及其他严重并发症。结论：使用重组组织型纤溶酶原激活剂溶栓治疗急性ST段抬高型心肌梗死,梗死相关血管再通率显著高于尿激酶,合并症少,安全性好。     

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinasetype plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P<.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P<0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P<0.01), lymph node metastasis and depth of invasion (P<0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.     

肿瘤患者胸水可溶性尿激酶受体检测及其临床意义

目的　了解良、恶性胸水中可溶性尿激酶受体 (suPAR)的水平及其与肿瘤患者病情和预后的关系。方法　放射免疫分析法检测 2 6例恶性胸水及 10例炎性胸水患者suPAR水平 ,并与 2 1名正常人 (对照组 )对照。结果　恶性胸水、炎性胸水与正常血浆suPAR水平分别为 (4 .3 6±2 .12 ) μg/L、(2 .64± 1.0 5 ) μg/L和 (1.73± 0 .96) μg/L ,炎性胸水suPAR水平高于对照组 (P <0 .0 5 ) ,而恶性胸水suPAR水平又高于炎性胸水 (P <0 .0 5 )。恶性胸水suPAR水平还显示出与患者预后相关。结论　检测suPAR水平有助于鉴别胸水的良、恶性及判断恶性肿瘤患者的预后     

Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma

BACKGROUND AND METHODS: The plasminogen activation system plays a crucial role in the process of cancer invasion and metastasis. To evaluate the most effective factor in the invasion, metastasis and prognosis of hepatocellular carcinoma (HCC), we examined urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1, PAI-2 and uPA activity by enzyme-linked immunosorbent assays (ELISA) in HCC tissues obtained from 46 patients. The results were compared with the patients' clinicopathological features and prognoses. RESULTS: Of the clinicopathological features, only histological portal involvement or intrahepatic metastasis, or both (INV), was significantly correlated to the disease-free survival rates (DFS; P < 0.05). The levels of uPA, PAI-1 and PAI-2 antigens were significantly associated with INV and histological grade. The DFS was not different, however, between cases with uPA, PAI-1 and PAI-2 values above and below the median. The high levels of uPA activity were closely related to INV (P < 0.001), and the activity gradually raised histological grades (P < 0.0001). The DFS was significantly different between patients with uPA activity below and above the median (0.70 ng/mL; P = 0.0092); it was also significantly different between such patients without INV (P < 0.05). CONCLUSIONS: Urokinase-type plasminogen activator activity may be the most sensitive factor affecting HCC invasion in the plasminogen activation system and a strong predictor for the recurrence of HCC. We suggest that cases with uPA activity of more than 0.70 ng/mL should be carefully followed up for possible HCC recurrence.     

尿激酶型纤维蛋白溶解酶原激活物及其受体在支气管哮喘中的表达和意义

目的测定支气管哮喘（哮喘）患者血浆和诱导痰中尿激酶型纤维蛋白溶解酶原激活物及其受体（u-PA、u-PAR）的水平,以探讨其在哮喘发病中的作用。方法用酶联免疫吸附法（ELISA）分别检测29例哮喘急性发作者（发作组）、26例缓解者（缓解组）和15例正常健康者（对照组）血浆和诱导痰中u-PA、u-PAR的水平,并分别进行外周血和诱导痰细胞计数和分类,同期测量肺功能（第一秒用力呼气肺活量占预计值％,FEV．％pred）,分析u-PA、u-PAR与嗜酸性粒细胞（EOS％）、FEV1％pred的相关性。结果发作组和缓解组血浆u-PAR水平[（650±154）ng／L,（677±189）ng／L],较对照组[（478±165）ng／L]明显升高（P〈0．01）;三组血浆u-PA水平[（98±20）ng／L,（90±20）ng／L,（88±23）ng／L]比较差异无统计学意义（P〉0．05）。发作组和缓解组诱导痰u-PAR水平[（766±272）ng／L,（700±271）ng]较对照组（516±197）ng／L明显升高（P〈0．05）;三组诱导痰u-PA水平[（287±235）ng／L,（251±276）ng／L,（239±322）ng／L]比较差异无统计学意义（P〉0．05）。发作组与缓解组u—PA、11-PAR水平与FEV。％pred无明显相关关系（P〉0．05）。发作组与缓解组诱导痰u-PAR水平与诱导痰EOS正相关（r分别为0．796,0．770,P〈0．05）。结论u—PAR参与了哮喘气道慢性炎症的病理生理过程,其作用与嗜酸性粒细胞有关。     

尿激酶型纤溶酶原激活物与冠心病临床类型的关系

目的 探讨冠状动脉粥样硬化性心脏病（冠心病）患者血清尿激酶型纤溶酶原激活物（urokinase-type plasminogen activator,uPA）浓度变化及临床意义.方法 根据临床表现和冠状动脉造影结果,173例患者分为ST段抬高性心肌梗死（ST-segment elevation myocardial infarction,STEMI）组（n=61）、非ST段抬高急性冠脉综合征（non-ST-segment elevation acute coronary syndrome,NSTE-ACS）组（n=29）、稳定型心绞痛（stable angina pectoris,SAP）组（n=41）、冠状动脉造影正常组（正常对照组,n=42）.酶联免疫吸附试验（ELISA）法测定血清uPA的质量浓度;免疫速率法检测血清高敏C反应蛋白（high-sensitivity Creaction protein,hs-CRP）的质量浓度.结果 （1）STEMI组、NSTE-ACS组、SAP组血清uPA质量浓度均高于正常对照组,差异有统计学意义（P＜0.05或P＜0.01）;STEMI组和NSTE-ACS组血清uPA质量浓度高于SAP组,差异有统计学意义（P＜0.05或P＜0.01）.（2）各组uPA表达特征与hs-CRP的表达特征一致.（3）相关性分析显示,STEMI组、NSTE-ACS组和SAP组血清uPA质量浓度与血清hs-CRP浓度呈正相关（r=0.347,P＜0.01;r=0.452,P＜0.01;r=0.172,P＜0.05）.结论 冠心病患者uPA活性增高,是严重冠状动脉病变的相关危险因素,在冠心病发生、发展中可能起着重要作用.     

恶性肿瘤患者血液中尿激酶型纤溶酶原激活系统测定的临床意义

目的 研究恶性肿瘤患者血液中尿激酶型纤溶酶原激活物（ＵＰＡ）及其特异性受体（ＵＰＡＲ）和纤溶酶原激活物掏抑制物－１（ＰＡＩ－１）含量对肿瘤转移和预后的影响。方法用ＥＬＩＳＡ法测定５０例恶性肿瘤患者和２０例正常人血液中ＵＰＡ、ＵＰＡＲ和ＰＡＩ－１含量。结果 淋巴瘤ＵＰＡ,肺癌ＵＰＡ、ＰＡＩ－１,食管癌、肠癌和乳腺癌ＵＰＡ、ＵＰＡＲ和ＰＡＩ－１均显著升高（Ｐ〈０．０５～０．０１）;肿瘤组中,中、晚期组     

Chromosomal localization of the human urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 genes: Implications in colorectal cancer

Abstract Activation of the proenzyme of urokinase (uPA) on the surface of cancer cells has been implicated in the initiation of focal proteolytic mechanisms that permit invasion and metastasis by colon cancers. The activity of uPA on the cell surface appears to be a function of the number of uPA-specific receptors (uPAR) and the extent of inhibition of uPA by plasminogen activator inhibitors (PAI). The mapping of the genes coding for uPAR, and for PAI-2, was performed to determine whether their chromosomal localization suggested their involvement in the genetic alterations associated with cancer cell DNA.
This study confirms the localization of the human urokinase plasminogen activator receptor gene to chromosome 19q and, using in situ hybridization, provides a precise localization to chromosome 19q13.2. In addition, our results confirm the previous allocation of the human plasminogen activator inhibitor-2 gene to a location 18q21.3 → 18q21.1, a location that corresponds to the commonest (>70%) somatic deletions found in colorectal carcinomas. The mapping of the uPAR and PAI-2 genes enables the elucidation of their possible involvement in the genetic alterations that determine the invasive and metastatic phenotypes in colorectal cancer.     

Diagnostic significance of measurement of the receptor for urokinase-type plasminogen activator on granulocytes and in plasma from patients with paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by the deficiency of all proteins anchored to the membrane by the glycosyl-phosphatidylinositol (GPI) anchor. The receptor for urokinase-type plasminogen activator (uPAR) also is attached to the cell membrane by a GPI anchor, and that soluble uPAR (suPAR) is present in plasma. In the present study, we measured uPAR, CD55, and CD59 on granulocytes by means of flow cytometry and suPAR in plasma by means of immunoradiometric assay. The subjects were 20 patients with PNH, 59 other patients with anemia, and 21 healthy individuals. In patients with PNH, both the mean fluorescence intensity and the positive percentage of fluorescence-activated granulocytes of uPAR, CD55, and CD59 were remarkably decreased, whereas in patients with other forms of anemia, except 2 patients with aplastic anemia, the results were not altered in comparison with those for the healthy individuals. The level of uPAR was reduced to the same extent as were those of CD55 and CD59 on the PNH-affected granulocytes. Some peak shape abnormalities (double peaks, peak tailing, or both) in the histogram of fluorescence intensity were also found in patients with PNH. The suPAR concentration of PNH plasma was 4.04+/-2.47 ng/mL, which was higher than that of the healthy individuals, 1.73+/-0.96 ng/mL (P < .01). The positive percentage of fluorescence-activated granulocytes was inversely associated with the plasma suPAR level in patients with PNH (r = -0.79, P < .01). Our data suggest that measurement of uPAR on granulocytes by means of flow cytometry and of suPAR in plasma by means of immunoradiometric assay are specific techniques for the diagnosis of PNH.     

尿激酶型纤溶酶原激活物途径在大鼠酒精性肝纤维化形成中的作用

目的 通过观察尿激酶型纤溶酶原激活物(uPA)及其抑制物(PAI-1)在大鼠酒精性肝纤维化形成中的动态变化,探讨uPA纤溶途径在酒精性肝纤维化形成中的作用.方法 雄性SD大鼠随机分为空白组、四氯化碳(CCl4)组和造模组.采用56度二锅头酒、玉米油、吡唑混合物灌胃联合腹腔注射CCl4橄榄油溶液(CCl4∶橄榄油=1∶3...