Stuies on the Mechanisms of Thrombus-formation and Thrombolysis with Special Referencies to Clinical Diagnosis, Treatment and Prophyraxis of Thrombosis

血栓形成和溶栓机制的研究，特别涉及血栓的临床诊断、治疗和预防

• 批准号: 60304065
• 负责人: TANAKA Kenzo
• 金额: $ 14.27万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60304065/
• 关键词: Thrombosis; Vascular endothelial cell; Platelet; Coagulation factor; Prostaglandine; Activating mechanism; Regulation mechanism; 蛋白化学; プラスミノゲン・アクチベーター; アクチベーター・インヒビター; 凝固・線溶系活性化ならびに制御機構

This project was co-operatively performed to elucidate the recent topics as the important factors participating in the thrombosis, namely cell-biological characteristics of endothelial cell function, risk factors of endothelial injuries, the molecular mechanism of platelet adherence and aggregation, biochemical and immunohistochemical studies of initiating and regulating factors of coagulation-fibrinolysis system. In addition, on these basic researches clinical or preclinical alterations of coagulatory and fibrinolytic functions were enzymologically and immunochemically analyzed for platelets and several factors of coagulation-fibrinolysis system. We established the immunoenzymatic and specific enzymatic assay methods for several serine-proteases and inhibitors.1. Studies on the mechanism of thrombus-formation and thrombolysis: Endothelial cells synthesized and expressed not only the antithrombogenic but also thrombogenic factors or functions. Factor VII, thrombomodulin, _2PI, protein C, protein S,PA inhibitor (type 1), acid-stable trypsin inhibitor and calphobindin were analyzed for immunochemical properties and/or amino acid and cDNA sequences.2. Studies on the pathogenesis, diagnosis and treatment of clinical thrombosis: The localization of glycoprotein I, IIb/IIIa was immunoultrastructurally investigated using collodal gold as a tracer. These membrane proteins were participated in platelet adherence and aggregation, associated with the thrombin and fibrinogen binding. ELISA systems for measuring cycloxygenase and 12-lipoxygenase in platelets were developed using MCAs. Oral and intravenous administrations of urokinase were effective for cerebrovascular thrombosis and acute myocardial infarction.

本课题旨在阐明近年来有关血栓形成的重要因素，即内皮细胞功能的细胞生物学特性、内皮损伤的危险因素、血小板粘附和聚集的分子机制、凝血纤溶系统启动因子和调节因子的生化和免疫组化研究。此外，在这些基础研究的临床或临床前的凝血和纤溶功能的变化进行了酶学和免疫化学分析的血小板和凝血-纤溶系统的几个因素。建立了几种丝氨酸蛋白酶和丝氨酸蛋白酶的免疫酶法和特异性酶法.血栓形成和溶栓机制的研究：内皮细胞不仅合成和表达抗血栓形成的因子或功能，而且合成和表达血栓形成的因子或功能。分析凝血因子VII、血栓调节蛋白、_2PI、蛋白C、蛋白S、PA抑制剂（1型）、酸稳定胰蛋白酶抑制剂和钙结合蛋白的免疫化学性质和/或氨基酸和cDNA序列.临床血栓形成的发病机制、诊断和治疗的研究：以胶体金为示踪剂，对糖蛋白I、IIb/IIIa的定位进行了免疫透射电镜研究。这些膜蛋白参与血小板粘附和聚集，与凝血酶和纤维蛋白原结合有关。用微阵列法建立了测定血小板中环氧合酶和12-脂氧合酶的ELISA系统。尿激酶口服和静脉给药对脑血管血栓形成和急性心肌梗死有效。

项目成果

Mimura, K.: Path. Res. Pract.IN PRESS.

Mimura, K.：路径。

Mimuro, J.: Blood. 69. 446-453 (1987)

三室，J.：血。

H.Tanaka;N.Kobayashi;T.Maekawa: Thrombos Haemostas. 56. 137-143 (1986)

H.Tanaka；N.Kobayashi；T.Maekawa：血栓止血。

Fukumoto, S.: Acta Pathol. Jpn.37. 1-9 (1987)

福本，S.：病理学报。

K.Suzuki;Y.Deyashiki;J.Nishioka;K.Kurachi;M.Akira;S.Yamamoto;S.Hashimoto: J Biol Chem. 262. 1-6 (1987)

K.Suzuki;Y.Deyashiki;J.Nishioka;K.Kurachi;M.Akira;S.Yamamoto;S.Hashimoto：J Biol Chem。