STIMULUS-RESPONSE COUPLING IN UREMIC PLATELETS

肾功能不全患者的止血功能可能严重受损， 疾病 我的假设是尿毒症的出血性疾病 患者是血小板功能障碍的结果，特别是关于 涉及血小板糖蛋白Ib（GPIb）的反应。 人们早就 接受GPIb是血管内皮细胞与血小板结合的主要位点， Willebrand因子（vWF），我们最近已经确定GPIb是 凝血酶激活血小板的受体。 为了检验这一假设，将进行以下研究：1） 尿毒症患者血小板GPIb结构完整性的测定 患者的电泳迁移率和碎片， 血小板Ca++依赖性蛋白酶和白细胞弹性蛋白酶。 这些研究 将确定GPIb中是否存在原发性结构异常 由于已知的蛋白酶或糖苷酶的作用， 存在于尿毒症血浆中或低分子量分子， 可以与GPIb共价结合。 2)尿毒症患者血浆的抗氧化能力研究 在正常血小板中诱导类似缺陷的成分，特别是 关于凝血酶和vWF的结合和激活。 3)如果这些 在尿毒症血小板中，这些过程已经受到损害，实验将 进行鉴定尿毒症血浆蛋白酶、糖苷酶或其他 导致这些变化的因素。 4)的作用机制进行了研究 凝血酶与尿毒症血小板，以确定他们是否减少 止血效果是GPIb自身结合缺陷的结果 或血小板兴奋中受体远端的缺陷 反应 凝血酶与尿毒症血小板结合的能力以及 诱发血小板活化将通过聚集、5-羟色胺 纤维蛋白原受体的释放和表达与正常对照组相比 血小板 5)尿毒症血小板与正常血管性血友病因子相互作用的研究 并确定尿毒症vWF的结构和功能完整性。 因此，在本发明中， 尿毒症血小板对vWF应答的能力以及 尿毒症vWF诱导正常血小板的反应， 确定。 可能的协同效应的组合缺陷， 将检查尿毒症GPIb和尿毒症vWF。

Hemostatic function may be severely compromised in patients with renal disease. It is my hypothesis that the bleeding disorders of uremic patients are the result of platelet dysfunction, particularly with regard to reactions involving platelet glycoprotein Ib (GPIb). It has long been accepted that GPIb is a primary site for the binding to platelets of von Willebrand Factor (vWF) and we have recently established that GPIb is the receptor for platelet activation by thrombin. In order to test this hypothesis, studies will be conducted to: 1) Determine the structural integrity of GPIb on platelets from uremic patients with regard to electrophoretic mobility and fragmentation by the platelet Ca++-dependent protease and leukocyte elastase. These studies will determine whether there are primary structural abnormalities in GPIb in uremic platelets due to the effects of proteases or glycosidases known to be present in uremic plasma or of low molecular weight molecules that may bind covalently to GPIb. 2) Study the ability of uremic plasma components to induce similar defects in normal platelets, particularly with regard to the binding of and activation by thrombin and vWF. 3) If these processes have been compromised in uremic platelets, experiments will be conducted to identify the uremic plasma protease, glycosidase or other components which cause these alterations. 4) Study the interaction of thrombin with uremic platelets to ascertain whether their reduced hemostatic effectiveness is a result of a defect in binding to GPIb itself or a defect distal to the receptor in the excitation of the platelet response. The ability of thrombin to bind to uremic platelets and to elicit platelet activation will be measured by aggregation, serotonin release and expression of fibrinogen receptors in comparison to normal platelets. 5) Study the interaction of normal vWF with uremic platelets and determine the structural and functional integrity of uremic vWF. Thus, the capacity of uremic platelets to respond to vWF as well as the ability of uremic vWF to induce a response in normal platelets will be ascertained. The possible synergistic effect of combined defects in the uremic GPIb and uremic vWF will be examined.