Absolute activated protein C concentration in acute ischemic stroke

急性缺血性脑卒中的绝对活化蛋白 C 浓度

基本信息

批准号：
09670672
负责人：
KITAGAWA Yasuhisa
金额：
$ 1.22万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

Activation of platelets and a hypercoagulable state generally occur in acute and chronic ischemic stroke. Protein C is activated to activated protein C (APC) by thrombin, which combines with thrombomodulin in endothelial cells. APC functions as an anticoagulant by inhibiting the activity of coagulation cofactors Va and VIIIa. The concentration of APC has been expressed as the % change or antigen values, not absolute values. The purpose of the present study was to determine the absolute values of the APC concentration and to assess their importance in acute ischemic stroke.We examined APC in 47 acute ischemic stroke patients, which included 21 with atherothrombotic infarction (ATI) (mean age 73), 15 with lacunar infarction (LI) (mean age 70) and 11 with cardiogenic embolism (CE) (mean age 80). The APC concentration was estimated by enzyme capture assay (ECA) (Teijin). Anti-Protein C monoclomal antibodies were immobilized in microplates, and the surface was blocked. Samples containing AP … More C and benzamidine, a reversible inhibitor of APC, were incubated in the wells for capture of APC antigen. Unbound sample constituents and the benzamidine were removed by extensive washing. The amidolytic activity of the captured APC was measured using a chromogenic substrate. The measurements were performed at the hyperacute (within 24 hours after onset), acute (4-7 days), subacute (8-14 days) and chronic (30 days) stages in each patient. Coagulant and fibrinolytic markers were determined simultaneously at each stage.The absolute APC concentration within 24 hours after onset was 3.3±0.9 in ATI, 2.5±0.8 in LI and 3,1±1.1 in CE. A significant difference was observed between ATI and LI (p<0.01), When the cases were divided into perforating artery infarction and cortical infarction, no significant difference in APC concentration was evident between them. As regards chronological changes of APC concentration, it tended to decline gradually with time in CE and ATI, but not in LI. We examined the relationship between coagulant and fibrinolytic markers and the APC concentration, and found a significant correlation between prothrombin fragment 1+2 and the APC concentration in CE (p<0.05). Concerning the severity of disease, no correlation existed between the APC concentration and NIH Stroke Scale scores.We determined the absolute concentration of APC in acute ischemic stroke patients for the first time. Elevation of the APC concentration was found in CE and ATI at the acute stage. The correlation between APC and prothrombin fragment 1+2 indicated that APC could represent one of the hypercoagulable markers in acute stroke. However, further research is needed to enhance the accuracy of measurement and to evaluate the most appropriate measuring time, especially at the acute stage. Supplementary administration of APC might provide a new therapy for acute ischemic stoke in the future. Less

血小板活化和高凝状态通常发生在急性和慢性缺血性中风中，凝血酶将蛋白 C 激活为活化蛋白 C (APC)，APC 与内皮细胞中的血栓调节蛋白结合，通过抑制凝血辅助因子的活性发挥抗凝作用。 Va 和 VIIIa。APC 的浓度表示为百分比变化或抗原值，而不是绝对值。本研究的目的是确定绝对值。我们检查了 47 名急性缺血性中风患者的 APC，其中包括 21 名患有动脉粥样硬化血栓性梗塞 (ATI) 的患者（平均年龄 73 岁），15 名患有腔隙性梗塞 (LI) 的患者（平均年龄 70 岁） ) ) 和 11 例心源性栓塞 (CE)（平均年龄 80 岁）通过酶捕获测定 (ECA) 估算 APC 浓度。 (Teijin) 将抗蛋白 C 单克隆抗体固定在微孔板中，并封闭含有 APC C 和苯甲脒（APC 可逆抑制剂）的样品，以捕获未结合的样品成分。使用显色底物测量捕获的 APC 的酰胺分解活性。发病后24小时）、急性（4-7天）、亚急性（8-14天）和慢性（30天）阶段同时测定每个患者的凝血和纤溶标志物。24小时内的绝对APC浓度。发病后ATI为3.3±0.9，LI为2.5±0.8，CE为3.1±1.1，ATI和LI之间观察到显着差异。 (p<0.01)，当病例分为穿支动脉梗塞和皮质梗塞时，APC浓度无明显差异。从APC浓度的时间变化来看，CE和ATI随时间的推移呈逐渐下降的趋势。但在 LI 中则不然。我们检查了凝血剂和纤溶标记物与 APC 浓度之间的关系，发现凝血酶原片段 1+2 与 CE 中的 APC 浓度之间存在显着相关性。 (p<0.05)。关于疾病的严重程度，APC浓度与NIH卒中量表评分之间不存在相关性。我们首次测定了急性缺血性卒中患者中APC浓度的升高。急性期的CE和ATI与凝血酶原片段1+2之间的相关性表明APC可以代表急性脑卒中的高凝标志物之一，但仍需进一步研究以提高准确性。并评估最合适的测量时间，特别是在急性期补充APC可能为未来的急性缺血性中风提供新的治疗方法。