组织纤溶酶原激活物和纤溶酶原激活物抑制剂-1与腹腔镜手术的关系

组织纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂-1(PA I-1)是纤溶系统的重要组成部分,传统开腹手术,t-PA与PA I-1之间的平衡被打破,导致术后腹腔粘连及血栓形成。腹腔镜手术对人体创伤小,对腹膜刺激少,因此,对t-PA和PA I-1之间的平衡影响减小,术后粘连及血栓形成的发生率及程度也随之降低。本文综述了t-PA和PA I-1与腹腔镜手术方面的研究进展。     

福辛普利钠对糖尿病肾脏病大鼠肾组织PAI-1表达的影响

目的观察福辛普利钠对糖尿病肾脏病（diabete kidney disease，DKD）大鼠PAI-I表达的影响。方法将45只Wistar大鼠随机分为3组，正常对照组（A组）13只，糖尿病组（B组）16只，福辛普利钠干预组（C组）16只。采用链脲佐菌素腹腔注射建立糖尿病模型。于第4、8、12周末各组随机选取4只大鼠处死并收集标本，记录体重、右肾重；检测血糖、血肌酐、血尿素氮、血胆固醇、血甘油三酯、24h尿蛋白排泄量。用逆转录PCR方法检测肾皮质PAI-1mRNA表达水平。结果造模成功，随时间增加，各组观察的指标有不同程度升高，但药物干预组与糖尿病组比较有不同程度下降。结论福辛普利钠可以抑制PAI-1 mRNA表达、延缓DKD的进展。     

组织纤溶酶原激活物和纤溶酶原激活物抑制剂-1与腹腔镜手术的关系

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）是纤溶系统的重要组成部分,传统开腹手术,t-PA与PAI-1之间的平衡被打破,导致术后腹腔粘连及血栓形成.腹腔镜手术对人体创伤小,对腹膜刺激少,因此,对t-PA和PAI-1之间的平衡影响减小,术后粘连及血栓形成的发生率及程度也随之降低.本文综述了t-PA和PAI-1与腹腔镜手术方面的研究进展.     

非创伤性股骨头坏死中纤溶酶原激活物抑制剂-1作用机制的研究进展

非创伤性股骨头坏死(nontraumatic osteonecrosis of the femoral head,NONFH)是好发于青壮年人群且致残率极高的骨科常见疾病,其发病机制尚未完全确定。纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1)作为一种重要的生理调节因子,在NONFH患者的血栓形成、纤维溶解能力减弱、血管生成减少、内皮损伤增加、骨细胞状态异常改变等病理活动中均起到重要作用。NONFH患者血清中的PAI-1水平存在特异性升高,这种改变可以作为无创性生物标志物用于NONFH的诊断。本文全面综述PAI-1与NONFH的关系以及PAI-1抑制剂在NONFH治疗上的潜在应用,提出PAI-1可以作为重要的NONFH治疗靶点,总结了多种PAI-1抑制剂的重要临床和科研价值。     

t-PA和PAI-1与腹腔镜手术的关系

t-PA和PAI-1是纤溶系统的重要组成部分,传统开腹手术,t-PA与PAI-1之间的平衡被打破,易导致术后腹腔粘连及血栓形成。腹腔镜手术对人体创伤小,腹膜刺激少,因此,对t-PA和PAI-1之间的平衡影响减小,术后粘连及血栓形成的发生率及程度也随之降低。     

t-PA/PAI-1在乙型肝炎病毒相关性肾炎中的表达及意义

目的：探讨t-PA/PAI-1在乙型肝炎病毒相关性肾炎（HBV-GN）中的表达及临床意义。方法：选择2002年～2004年间获得的100例HBV-GN肾活检标本为实验对象,运用免疫组化方法观察HBV-GN肾组织t-PA/PAI-1的表达特点,并统计分析其与病理类型、肾小球病变程度及临床指标之间的关系。结果：各病理类型组t-PA/PAI-1阳性积分差异无统计学意义（P〉0.05）;而在不同的肾小球病变等级中,Ⅱ级、Ⅲ级组t-PA阳性积分开始升高,以Ⅲ级组最高（P〈0.05）,Ⅳ级组积分下降（P〈0.05）;PAI-1随肾小球病变等级的增加阳性积分升高（P〈0.05,P〈0.01）,并随肾功能减退阳性积分增高（P〈0.05,P〈0.001）。结论：t-PA/PAI-1在乙肝肾中的表达平衡失调促进肾小球硬化;肾组织内PAI-1随肾功能减退而表达增强,可能是HBV-GN预后不良的指标之一。     

肾病综合征患者血浆中t-PA/PAI-1的变化及糖皮质激素治疗的影响

目的:探讨肾病综合征患者糖皮质激素治疗前后不同阶段组织型纤溶酶原激活物(t-PA)与纤溶酶原激活物抑制物-1(PA1-1)的变化.方法:分为健康对照组、肾病综合征组,采用酶联免疫吸附(ELISA)方法检测血浆中t-PA和PAI-1水平的变化.结果:t-PA的血浆水平在各组之间无统计学差异(P>0.05);PAI-1的水平在肾病综合征组较正常明显升高(P<0.05),激素治疗1周后进一步升高(P<0.05),治疗4周后比1周组有显著下降(P<0.05),但较正常仍高(P<0.05).结论:t-PA/PAI-1平衡的紊乱,可能参与了肾病综合征的损伤机制,经糖皮质激素治疗后高凝状态短期内无明显改善.     

血清t-PA和PAI-1水平在腹腔镜手术中的临床意义

目的:探讨腹腔镜与开腹手术中血浆纤维蛋白溶酶的变化。方法:在腹腔镜与开腹手术前、术后8h分别测量血浆中组织型纤溶酶原激活物(Tissue-type p lasm inogen activator,t-PA),纤溶酶原激活物抑制物-1(P lasm inogen activator inh ib itortype-1,PAI-1)浓度。结果:血浆t-PA浓度在腹腔镜手术和传统腹部手术两组病例术后均下降,但在传统腹部手术组下降更显著(P<0.05),而血浆PAI-1浓度在腹腔镜手术和传统腹部手术两组病例术后均升高,但在传统腹部手术组升高更显著(P<0.05)。结论:本次临床研究结果表明:腹腔镜手术组术前、术后血浆中t-PA、PAI-1浓度的变化小于传统腹部手术组,腹腔镜手术组引起腹腔粘连严重程度也低于传统腹部手术组。     

肾小管间质纤维化大鼠u-PA/PAI-1的表达及桂枝茯苓胶囊对其影响

目的：观察桂枝茯苓胶囊对肾小管间质纤维化（tubulointerstitial fibrosis,TIF）的肾组织中的尿激酶型纤溶酶原激活物（urokinase-type plasminogen activator,u-PA）及纤溶酶原激活物抑制剂-1（plasminogen activator inhibitor-1,PAI-1）表达的影响。方法：雄性3月龄SD大鼠72只,随机分为：假手术组（24只）,模型组（24只）,预防组（24只）。行单侧输尿管结扎术单侧输尿管梗阻诱导TIF模型。预防组大鼠加以125 mg/kg桂枝茯苓胶囊,溶于生理盐水灌胃,日2次,模型组及假手术组每天以等体积生理盐水灌胃。各组分别于实验第7天、第14天、第21天时随机选取8只大鼠,处死后行光镜下观察梗阻侧肾脏组织病理学改变、免疫组织化学法（SP法）评价肾脏尿激酶型纤溶酶原激活物-PA、PAI-1表达变化。结果：（1）PAI-1表达量在假手术组各时间点差异无统计学意义（P〉0.05）。各时间点模型组、预防组均高于假手术组（P〈0.01,P〈0.05）,除PAI-1表达量在7 d时模型组与预防组无明显差异外,预防组均低于模型组（P〈0.01）。模型组、预防组表达量随梗阻时间延长而增加（P〈0.01,P〈0.05）。（2）各时间点预防组u-PA表达量均低于假手术组（P〈0.01）,高于模型组（P〈0.01,P〈0.05）。模型组、预防组14 d、21 d u-PA的表达量均较各自前一时间点减少（P〈0.01）,假手术组u-PA的表达量各时间点差异无统计学意义（P〉0.05）。（3）肾小管间质损害半定量评分与PAI-1（r=0.917,P〈0.01）表达量呈正相关,与u-PA表达量呈负相关（r=-933,P〈0.01）。结论：桂枝茯苓胶囊能减轻梗阻肾组织的病理损害,延缓TIF的进程。并参与纤维化形成的全过程。     

高脂饮食小鼠脂肪组织中PAI-1、FOXC2及FOXO1表达的研究

目的：研究高脂饮食喂养小鼠内脏脂肪和皮下脂肪组织中PAI-1、FOXC2及FOXO1表达水平,探讨不同类型肥胖的机制。方法20只小鼠随机分为对照组和高脂组,分别给予正常饮食和高脂饮食喂养12周。测定血清PAI-1以及附睾周围组织及皮下脂肪中PAI-1、FOXC2及FOXO1 mRNA的表达水平。结果高脂组小鼠体质量、血清PAI-1水平均显著高于对照组。组内比较小鼠附睾周围脂肪组织PAI-1、FOXC2mRNA表达显著高于皮下脂肪组织;FOXO1mRNA表达显著低于于皮下脂肪组织,差异有统计学意义。结论正常体重小鼠和肥胖小鼠血清PAI-1水平表达不同,内脏脂肪和皮下脂肪PAI-1、FOXC2及FOXO1表达也存在差别,这种差别可能是不同类型肥胖的机制之一。     

Changes in osmolality during liquefaction of human semen

The osmolality of 18 liquefying human semen samples from 15 volunteers was measured by vapour pressure osmometry to be low (294 mmol/kg, range 269-311). For each sample the osmolality increased during liquefaction to reach a mean of 312 mmol/kg (280-331) by 30 min at 37 degrees C. These results are at variance with the widely held view that semen osmolality is greater than that of serum, which results from its first being examined after liquefaction in vitro. Thus when sperm are routinely examined after liquefaction they have been subjected to osmotic stresses that are not experienced by spermatozoa entering the female tract at coitus.     

Inhibition of liquefaction and protein degradation in human semen by gossypol

The liquefaction of freshly ejaculated human semen was delayed by gossypol. Liquefaction is normally accompanied by an autolytic degradation of semen proteins, and prior incubation with gossypol can inhibit factors (presumably proteinases) present in seminal plasma that degrade semen proteins. The possible consequences of this inhibition are discussed in relation to the proposed use of gossypol as a vaginal contraceptive.     

尿激酶型纤溶酶原激活因子及其受体在神经母细胞瘤中的表达及其意义

目的：研究尿激酶型纤溶酶原活因子（uPA)及其受体（uPAR）在神经母细胞瘤（NB）中的表达和意义。方法：应用免疫组织化学方法研究uPA及uPAR在42例神经母细胞瘤中的表达，并应用逆转录-聚合酶链式反应（RT－PCR）方法检测患儿骨髓和外周血中的神经蛋白基因产物9．5（PGP9．5）。结果：uPA及uPAR阳性表达主在进展期肿瘤（均为85．7％）高于局灶期肿瘤（42．9％，28．6％）；预后不良型患儿（91．7％，83．3％）高于预后良好型患儿（均为44．4％），且差异均具有非常显著性（P＜0．01）。患儿骨髓和外周血中PGP9．5阳性检出率在uPA阳性患儿组（60．0％）显著高于uPA阴性患儿组（8．3％，P＜0．01）；uPAR阳性组（57．1％）高于uPAR阴性组（21．4％，P＜0．05）。uPA和uPAR同时阳性的10例患儿，骨髓和外周血中均有PGP9．5阳性表达，而同时阴性的5例患儿中，均未检测到PGP9．5。结论：uPA和uPAR在NB的浸润转移过程中发挥重要的作用。     

脉血康对单侧输尿管梗阻大鼠肾保护作用及机制探讨

目的观察脉血康对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾脏保护作用并探讨其可能作用机制。方法建立UUO大鼠模型,大鼠随机分为假手术组、模型组及脉血康组3组,各组给予相应干预,各组大鼠于术后14 d处死,抽取血清并留取肾组织标本,检测各组大鼠血肌酐(SCr)、尿素氮(BUN)、胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)情况,并观察各组肾脏病理改变情况,采用免疫组化方法观察肾组织中组织型纤溶酶原激活物(tissue type plasminogen activator,t-PA)、尿激酶型纤溶酶原激活物(urokinase type plasminogen activator,u-PA)、纤溶酶原激活物抑制剂1(plasminogen activator inhibitor-1,PAI-1)在各组的表达情况。结果①3组肾脏形态学变化有差异,假手术组双肾大小及体积无改变,颜色红润,模型组及脉血康组术侧肾脏体积明显增大,术侧肾盂肾盏及输尿管结扎段以上全程扩张。模型组肾实质颜色变浅,剖面肾皮质变薄,皮髓质分界不清,脉血康组肾脏颜色稍红润,肾脏皮髓质分界较清。②假手术组肾脏病理未见明显改变,与假手术组比较,模型组及脉血康组肾小管损伤及肾间质纤维化程度显著(P0.01);与模型组比较,脉血康组肾小管损伤及肾间质纤维化程度明显减轻(P0.05)。③与假手术组相比,模型组SCr、BUN、TC、TG水平均升高(P0.05),与模型组相比,脉血康组SCr、BUN、TC、TG水平均下降(P0.05)。④假手术组PAI-1、t-PA、u-PA表达于肾小管上皮细胞及肾小球系膜细胞胞浆,肾间质表达极少;与假手术组比较,模型组及脉血康组PAI-1明显增多(P0.05),而t-PA、u-PA表达明显减少(P0.05),与模型组相比,脉血康组PAI--1表达明显减少,t-PA表达明显增多(P0.05),u-PA无明显差别(P0.05)。结论脉血康可能通过调节脂质代谢下调肾脏PAI-1的表达,上调t-PA的表达从而促进肾脏细胞外基质降解,对UUO大鼠肾间质纤维化及肾功能具有保护作用。     

Initiation of a fibrinolytic system in hepatic resection: The roles of tissue-type plasminogen activator and plasminogen activator inhibitor-1

The factors related to the initiation of fibrinolysis, especially with regard to the tissue-type plasminogen activator (tPA) and the plasminogen activator inhibitor-1 (PAI-1), were investigated in 15 patients who underwent hepatic resection, and the findings were compared between those with normal livers and those with diseased livers. It was found that tPA increased before hepatic division, whereas PAI-1 increased after hepatic division and reached a peak immediately following the operation. Plasminogen decreased during hepatectomy, reaching its lowest point on postoperative day 1, and increasing later. Decreased levels of both plasminogen and the ₂-plasmin inhibitor were considered to be partly due to plasmin formation in the blood. Patients with a diseased liver tended to have higher intraoperative values of euglobulin lysis activity and higher postoperative values of plasminogen activator, but significantly lower postoperative values of ₂-plasmin inhibitor than those with a normal liver. The results of this study suggest that activation of the fibrinolytic system occurs both during hepatectomy and in the early postoperative period, and that patients with a diseased liver are prone to develop hyperfibrinolysis during hepatectomy. Moreover, the increased levels of both tPA and PAI-1 can serve as one of the most sensitive markers for the vital reaction against surgical stress.     

PAI－1、t-PA、u—PA、u—PAR在支气管哮喘患者诱导痰中的表达及意义

目的探讨纤维蛋白溶解酶原激活物抑制剂（PAI）－1、组织型纤维蛋白溶解酶原激活物（t—PA）、尿激酶型纤维蛋白溶解酶原激活物（u－PA）及其受体（u－PAR）在支气管哮喘（简称哮喘）患者诱导痰中的表达及意义。方法用ELISA法分别检测29例哮喘急性发作者（发作组）、26例缓解者（缓解组）及15例健康对照者（对照组）诱导痰中PAI－1、t-PA、u—PA和u－PAR的含量,同期测定肺功能（第1秒用力呼气容积占预计值百分比,FEV,％pred）,并进行比较。结果发作组和缓解组诱导痰PAI－1、u—PAR含量[分别为（23．32±2t．64）、（0．766±0．272）μg／L和（17．23±9．40）、（0．700±0．271）μg／L]较对照组[（5．99±5．04）、（O．516±0．197）μg／L3均明显升高（P〈0．05）。而三组诱导痰u—PA、t-PA含量[分别为（O．287±0．235）、（7．68±3．46）μg／L,（0．251±0．276）、（9．88±4．68）μg／L,（0．239±0．322）、（10．35±7．47）μg／L]比较差异均无统计学意义（P〉0．05）。缓解组诱导痰PAI-1与FEV1 % pred呈负相关（r=-0．756,P〈0．01）。缓解组诱导痰PAI-1与病程呈正相关（r=0．454,P〈0．05）。结论PAI-1、u-PAR参与了哮喘气道慢性炎性反应的病理生理过程。     

Increased plasminogen activator activity and plasminogen activator inhibition in spermatozoa and seminal plasma of the ram after serum gonadotrophin (PMSG) administration. Correlation with the increased level of testosterone in the blood

After a single injection of serum gonadotrophin (PMSG) at the dose of 15 IU/kg, i.m. into rams testosterone in the plasma of blood showed a significant rise between 4th and 7th day post-injection. At the same time (4th-7th day) the plasminogen activator activity (PAA) in seminal plasma was found to be increased, but the plasminogen activator inhibition (PAI) expressed against t-PA (anti-t-PA) showed an increase between 32nd and 46th day. In spermatozoa a marked increase of PAA was revealed between 32nd and 46th day post-injection, while an increase of PAI (anti-t-PA) was exhibited on the 74th day. Plasmin inhibition (PI) in seminal plasma and spermatozoa showed no change compared to controls. A positive correlation has been found between increased concentrations of testosterone and PAA or PAI (anti-t-PA) in spermatozoa and seminal plasma. The induced increase of PAA in spermatozoa under the effect of testosterone might be of physiological importance, since PAA is localized to sperm membranes and might participate in the whole process of fertilization.     

Thrombospondin-1 and transforming growth factor beta-1 upregulate plasminogen activator inhibitor type 1 in pancreatic cancer

Controlled degradation of the extracellular matrix by proteases is crucial in tumor cell invasion. We have shown that thrombospondin-1 (TSP-1), through activation of transforming growth factor beta-1 (TGF-β1), regulates the plasminogen/plasmin protease system in breast cancer. To determine whether this occurred in other epithelial neoplasms, we studied the role of TSP-1 and TGF-β1 in the regulation of the plasminogen/plasmin system in pancreatic cancer. ASPC-1 and COLO-3S7 pancreatic cancer cells were treated with TSP-1 or TGF-β1 at varying concentrations. The TSP-1 and TGF-β1-treated cells were also treated with either anti-TSP-1, anti-TSP-1 receptor, or anti-TGF-β1 antibodies. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression was determined by enzyme-linked immunosorbent assay. TSP-1 and TGF-β1 promoted a dose-dependent upregulation of ASPC-1 and COLO-3S7 PAI-1 expression. The TSP-1 effect could be blocked with anti-TSP-1 or anti-TGF-β1 antibodies. The TGF-β1 effect could be blocked only with anti-TGF-β1 antibody. Anti-TSP-1 receptor antibody blocked the TSP-1 effect on PAI-1 expression but had no effect on TGF-β1-mediated PAI-1 expression. Neither TSP-1 nor TGF-β1 had an effect on uPA production. We conclude that TSP-1, in a receptor-mediated process that involves the activation of TGF-β1, upregulates PAI-1 expression in pancreatic cancer without an effect on uPA production. Supported in part by National Institutes of Health grants CA65675 and CA69722 (Dr. Tuszysnki). Dr. Berger is the recipient of an American Cancer Society Clinical Career Development Award 96-09. Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14,1997.