Analysis of mechanism on enhancement of fibrinolysis as biological defense

增强纤维蛋白溶解的生物防御机制分析

• 批准号: 13470519
• 负责人: WADA Hideo
• 金额: $ 6.46万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470519/
• 关键词: old age; fibrinolysis; tPA; PAI-I; TAFI; PAI-I polymorphism; DIC; t-PA-PAI-I complex; PAI-Iプロモーター領域ポリモルフィズム

The prevention of the thrombosis in the old people becomes an important problem. The aging seemed to be large risk of the thrombosis, and we examined the relation between hemostasis abnormality and aging. In the examination of the maintenance dialysis patient, the death and crisis frequency which accompanied thrombosis increased with the aging. With the aging, there were calcification of the aorta and progress of the arteriosclerosis. In more than 70 years old of healthy volunteer, antithrombin and protein C reduced and thrombin- antithrombin complex and soluble fibrin levels were increased. While, in those, fibrinogen and fibrin degradation products and plasmin- plasmin inhibitor complex levels were increased, suggesting that hyperfibrinolysis exist in old peoples. However old health peoples had no secondary fibrinolysis due to thrombosis. These results indicated that physiological enhancement in fibrinolytic system was caused by aging. There are plasminogen activator (t-PA), plasmino … More gen activator inhibitor (PAI)-I, II, III and thrombin activatable fibrinolysis inhibitor (TAFI) in regulatory system of fibrinolysis. We established the usefulness of measurement in total PAI-I, tPA-PAI-I complex, TAFI and tPA by ELISA for the diagnosis of disseminated intravascular coagulation (DIG), deep vein thrombosis (DVT), and multiple organ failure (MOF) and acute myocardial infarction. As plasma levels of total PAI-I and TAFI were increased in old peoples, these factors may play an important role of the onset in thrombosis. It was suggested that elevated plasma levels of PAI-I was related to the polymorphism of promoter in PAI-I gene (4G/5G). After informed consent, the polymorphism of promoter in PAI-I gene (4G/5G) was examined in old peoples.There was no significant difference of distribution in the polymorphism between young peoples and old peoples. Our results showed no relationship between polymorphism of PAI-I gene promoter and thrombosis in old peoples. Finally, old peoples had high risk for thrombosis and significant atherosclerosis, however they were in hyperfibrinolytic state. Less

老年人血栓的预防成为一个重要的问题。年龄似乎是血栓形成的大风险，我们研究了止血异常与年龄的关系。在维持性透析患者中，随着年龄的增长，伴随血栓形成的死亡和危象频率增加。随着年龄的增长，主动脉钙化，动脉硬化程度加重。在70岁以上的健康志愿者中，抗凝血酶和蛋白C降低，凝血酶-抗凝血酶复合物和可溶性纤维蛋白水平升高。而纤维蛋白原、纤维蛋白降解产物及纤溶酶-纤溶酶抑制物复合物水平增高，提示老年人存在纤溶亢进。而老年健康人则无血栓形成引起的继发性纤溶。这些结果表明，纤溶系统的生理增强是由衰老引起的。有纤溶酶原激活物（t-PA）、纤溶酶 ...更多信息 纤溶调节系统中的纤溶酶原激活物抑制剂（PAI）-Ⅰ、Ⅱ、Ⅲ和凝血酶激活的纤溶抑制剂（TAFI）。我们建立了ELISA法测定总PAI-Ⅰ、tPA-PAI-Ⅰ复合物、TAFI和tPA对诊断弥散性血管内凝血（DIG）、深静脉血栓形成（DVT）、多器官功能衰竭（MOF）和急性心肌梗死的有效性。老年人血浆总PAI-Ⅰ和TAFI水平升高，提示这些因素在血栓形成中起重要作用。提示血浆PAI-Ⅰ水平升高与PAI-Ⅰ基因启动子区多态性（4G/5G）有关。在知情同意后，检测老年人PAI-Ⅰ基因启动子区（4G/5G）多态性，青年人与老年人PAI-Ⅰ基因启动子区（4G/5G）多态性分布无明显差异。结果表明PAI-Ⅰ基因启动子区多态性与老年人血栓形成无相关性。最后，老年人血栓形成和动脉粥样硬化的风险高，但他们处于高纤溶状态。少

项目成果

0hta S, Wada H, et al: "Evaluation of tissue factor antigen level in human seminal plasma"Urol Res. 30. 317-320 (2002)

0hta S，Wada H，等人：“人精浆中组织因子抗原水平的评估”Urol Res。

Tamaki S, Wada H, et al: "Hemostatic abnormalities following bone marrow transplantation"Clin Appl Thromb Hemost. 8. 125-132 (2002)

Tamaki S、Wada H 等人：“骨髓移植后的止血异常”Clin Appl Thromb Hemost。

Nakasaki T, Wada H, et al.: "Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer"Am J Hematol. (in press)(印刷中). (2002)

Nakasaki T、Wada H 等人：“组织因子和血管内皮生长因子的表达与结直肠癌中的血管生成有关”Am J Hematol（出版中）。

Wada H, Mori Y, et al.: "High plasma levels of fibrinogen are associated with poor outcome"Am J Hematol. 72・1. 1-7 (2003)

Wada H、Mori Y 等人：“高血浆纤维蛋白原水平与不良结果相关”Am J Hematol. 72·1 (2003)。

Kitai T, Nishikawa M, Tanigawa T, Okinaka T, Wada H, et al: "Inhibition by combined therapy with ticlopidine and aspirin of enhanced platelet aggregation during physical exercise in patients with coronary,artery disease"Am Heart J. 142. (2001)

Kitai T、Nishikawa M、Tanikawa T、Okinaka T、Wada H 等人：“在患有冠状动脉疾病的患者中，通过使用噻氯匹定和阿司匹林联合治疗对增强的血小板聚集进行抑制”Am Heart J. 142（2001 年）