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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670672/
• 关键词: ischemic stroke; activated protein C; anticoagulant; atherothrombotic infarction; cardiogenic embolism; prothrombin fragment 1+2; 血液凝固阻止因子; 心原性脳塞栓症; トロンビンアンチトロンビンIII複合体

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卒中中。蛋白C被凝血酶激活为活化蛋白C（APC），APC在内皮细胞中与血栓调节蛋白结合。APC通过抑制凝血辅因子Va和VIIIa的活性而起到抗凝剂的作用。APC浓度表示为%变化或抗原值，而不是绝对值。本研究的目的是确定APC浓度的绝对值，并评估其在急性缺血性卒中中的重要性，我们检测了47例急性缺血性卒中患者的APC，其中包括21例动脉粥样硬化血栓性梗死（ATI）（平均年龄73岁），15例腔隙性梗死（LI）（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）（帝人公司（Teijin））估计APC浓度。将抗蛋白C单克隆抗体固定在微孔板中，并封闭表面。含AP的样品 ...更多信息 C和苯甲脒（APC的可逆抑制剂）在威尔斯孔中孵育以捕获APC抗原。通过充分洗涤除去未结合的样品组分和苯甲脒。使用显色底物测量捕获的APC的酰胺分解活性。在每例患者的超急性期（发病后24小时内）、急性期（4-7天）、亚急性期（8-14天）和慢性期（30天）进行测量。发病后24小时内APC绝对浓度ATI为3.3±0.9，LI为2.5±0.8，CE为3.1 ±1.1。ATI与LI之间有显著性差异（p<0.01）。将AMI分为穿通动脉梗死与皮质梗死时，二者之间APC浓度无显著性差异。APC浓度随时间的变化，CE和ATI呈逐渐下降趋势，而LI则无此趋势。我们检查了凝血和纤溶标志物与APC浓度之间的关系，发现CE中凝血酶原片段1+2与APC浓度之间存在显著相关性（p<0.05）。就疾病的严重程度而言，APC浓度与NIH中风量表评分之间不存在相关性。我们首次测定了急性缺血性中风患者APC的绝对浓度。急性期CE和ATI的APC浓度升高。APC与凝血酶原片段1+2之间的相关性表明，APC可作为急性脑卒中高凝状态的标志物之一。然而，需要进一步的研究来提高测量的准确性，并评估最合适的测量时间，特别是在急性期。APC的辅助治疗可能为急性缺血性斯托克的治疗提供新的思路。少

项目成果

北川泰久: "脳梗塞における活性化プロテインC血行動態に関する検討" 脳卒中. 20巻1号. 211 (1998)

北川康久：“脑梗塞中活化蛋白C血流动力学的研究”，《中风》，第20卷，第1.211期（1998年）。