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RELEASABLE PLATELET PLASMINOGEN ACTIVATOR-INHIBITOR

可释放的血小板纤溶酶原激活剂抑制剂

基本信息

批准号：
3352056
负责人：
ROGER C CARROLL
金额：
$ 9.04万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 1990-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3352056
关键词：
affinity chromatography antifibrinolytic agents enzyme inhibitors enzyme linked immunosorbent assay enzyme substrate complex fibrinogen gel electrophoresis high performance liquid chromatography human subject immunochemistry laboratory rabbit plasminogen activator platelets postoperative complications protein C thromboembolism thrombospondins urokinase

项目摘要

Venous thrombo-embolism and deep vein thrombophlebitis are major causes of post-surgical morbidity and mortality. For a variety of reasons, history and physical exam, intravenous phlebography, and I-125 iodine uptake are either not reliable enough or have too much risk-associated invasiveness to be used in the screening for DVT, especially in equivocal situations. Nor are there well-identified, specific risk factors one can determine as predisposing the surgical patient toward developing thrombotic complications. The long-term objectives of this study are to determine the possible roles of releasable platelet plasminogen activator-inhibitor (PA-inhibitor) in the post-surgical development of thrombosis and to develop a functional assay for the PA-inhibitor which could be used to follow the post-surgical changes in plasma PA-inhibitor levels. Specific aims toward meeting these objectives are to: 1) purify in a native form the releasable platelet PA-inhibitor using lectin affinity and HPLC column chromatography; 2) characterize the interaction of this purified PA-inhibitor with other platelet releasate proteins such as fibrinogen or thrombospondin by imunoprecipitation and SDS-gel electrophoresis and determine whether these interactions are important in modifying the kinetics of inhibition of plasminogen activators and/or activated protein C; and, 3) develop a functional assay of plasma PA-inhibitor levels based on ELISA plates coated with urokinase in place of antibodies and to use this assay to follow the post-surgical kinetics of PA-inhibitor levels. The results from this studies could provide the basis for a more extensive application to correlate elevated functional PA-inhibitor levels with post-surgical deep vein thrombosis.

静脉血栓栓塞和深静脉血栓性静脉炎是引起术后发病率和死亡率。由于各种原因，历史体格检查、静脉内静脉造影和I-125碘摄入量是要么不够可靠，要么有太多与风险相关的侵入性，用于DVT的筛查，尤其是在可疑的情况下。也不是否有明确的，具体的风险因素，可以确定为使手术患者易于发生血栓形成并发症本研究的长期目标是确定可能的作用释放性血小板纤溶酶原激活物抑制剂（PA抑制剂）术后血栓形成的发展，并制定一个功能 PA抑制剂的测定，其可用于跟踪术后血浆PA抑制剂水平的变化。达到这些目标的具体目标是：1）在一个使用凝集素亲和力的天然形式的可释放的血小板PA抑制剂， HPLC柱色谱法; 2）表征这种相互作用纯化的PA-抑制剂与其他血小板释放蛋白，免疫沉淀法和SDS-凝胶法测定纤维蛋白原或血小板反应蛋白电泳，并确定这些相互作用是否是重要的改变纤溶酶原激活剂的抑制动力学，和/或活化蛋白C;和，3）开发血浆的功能测定 PA-抑制剂水平基于用尿激酶代替抗体，并使用该测定法来跟踪 PA抑制剂水平。这项研究的结果可以提供基础，对于更广泛的应用， PA抑制剂水平与术后深静脉血栓形成