RELEASABLE PLATELET PLASMINOGEN ACTIVATOR-INHIBITOR

可释放的血小板纤溶酶原激活剂抑制剂

• 批准号: 3352055
• 负责人: ROGER C CARROLL
• 金额: $ 8.88万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3352055
• 关键词: affinity chromatography; antifibrinolytic agents; enzyme linked immunosorbent assay; enzyme substrate complex; fibrinogen; gel electrophoresis; high performance liquid chromatography; human subject; immunochemistry; plasminogen activator; platelets; postoperative complications; protein C; thromboembolism; urokinase

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.

静脉血栓栓塞症和深静脉血栓性静脉炎是主要原因 手术后发病率和死亡率。出于各种原因，历史 体检，静脉静脉造影术和I-125碘摄取 要么不够可靠，要么具有太多与风险相关的侵入性 用于DVT的筛查，特别是在可疑情况下。非 是否有明确的、具体的风险因素可以确定为 使外科病人易患血栓形成 并发症。 这项研究的长期目标是确定可能的角色 可释放型血小板纤溶酶原激活物抑制物(PA抑制物)的研究 术后血栓形成的发展及功能性 可用于术后随访的PA-抑制物检测 血浆纤溶酶原激活物抑制物水平变化。 实现这些目标的具体目标是：1)在 利用凝集素亲和力和亲和力形成可释放的血小板PA抑制物 高效液相色谱柱层析；2)表征相互作用 纯化的PA抑制物与其他血小板释放蛋白，如 免疫沉淀法和十二烷基硫酸钠-凝胶法测定纤维蛋白原或凝血酶原 并确定这些相互作用是否在 修改纤溶酶原激活剂和/或抑制的动力学 活性蛋白C；以及，3)建立血浆功能分析方法 基于包被尿激酶的酶联免疫吸附试验平板的PA抑制物水平 并利用这一检测方法来跟踪术后的动力学 PA-抑制物水平。本研究的结果可以为研究提供依据。 对于更广泛的应用，以关联提升的功能 PA抑制物水平与术后深静脉血栓形成的关系。