MECHANISMS OF CORONARY REOCCUSION AFTER THROMBOLYTIC THERAPY-EFFECTS OF TISSUE TYPE PLASMINOGEN ACTIVATOR AND UROKINASE ON HUMAN LEUKOCYTES ACTIVATION,PLATELETS ACTIVATION AND THROMBIN GENERATION

溶栓治疗后冠状动脉再粘连的机制——组织型纤溶酶原激活剂和尿激酶对人白细胞激活、血小板激活和凝血酶生成的影响

• 批准号: 08670823
• 负责人: AOKI Nobuo
• 金额: $ 0.77万
• 依托单位: KYORIN UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670823/
• 关键词: P-selectin; tissue-type plasminogen activator; urokinase; acetylsalicylic acid; P-セレクチン; thrombolysis; P-selectin; Urokinase; tissue plasminogen activator

By measuring platelet surface P-selectin as a marker of platelet activation, the activation effects of tissue-type plasminogen activator and urokinase and the inhibitory effects of acetylsalicylic acid were investigated. After addition of urokinase (final concentration : 192 U/ml, 1,920 U/ml, or 19,200 U/ml) or tissue-type plasminogen activator (final concentration : 120 U/ml, 1,200 U/ml, or12,000 U/ml) to platelet-rich plasma from 12 healthy individuals, platelet-rich surface P-selectin expression was measured by flow cytometry using an anti-CD62 monoclonal antibody. Urokinase and tissue-type plasminogen activator increased platelet surface P-selectin expression in a concentration-dependent manner. Next, either 160 mg/day (n=6) or 660 mg/day (n=6) of acetylsalicylic acid were administered to the 12 healthy individuals, and venous blood samples were collected after 7 days of treatment. Platelet surface P-selectin expression was then measured by the same method before and after addition of tissue-type plasminogen activator or urokinase. Although the effect of acetylsalicylic acid at 160 mg/day on P-selectin expression was minimal, a dose of 660 mg/day supressed platelet surface P-selectin expression significantly and also significantly inhibited the platelet activating effects of tissue-type plasminogen activator and urokinase. From these findings, it was concluded that platelets were activated by tissue-type plasminogen activator or urokinase, and that platelet activation could be supressed by administering acetylsalicylic acid at 660 mg/day.

通过测定血小板表面p选择素作为血小板活化标志物，考察组织型纤溶酶原激活剂和尿激酶的活化作用以及乙酰水杨酸的抑制作用。将尿激酶（终浓度：192 U/ml、1920 U/ml或19200 U/ml）或组织型纤溶酶原激活剂（终浓度：120 U/ml、1200 U/ml或12000 U/ml）加入12名健康人富血小板血浆后，用抗cd62单克隆抗体流式细胞术检测富血小板表面p -选择素的表达。尿激酶和组织型纤溶酶原激活剂以浓度依赖的方式增加血小板表面p选择素的表达。接下来，12名健康个体分别给予160 mg/天（n=6）或660 mg/天（n=6）乙酰水杨酸，并在治疗7天后采集静脉血样本。然后用同样的方法测定加入组织型纤溶酶原激活剂或尿激酶前后血小板表面p选择素的表达。虽然160 mg/天乙酰水杨酸对p -选择素表达的影响很小，但660 mg/天剂量显著抑制血小板表面p -选择素表达，也显著抑制组织型纤溶酶原激活剂和尿激酶的血小板活化作用。由此得出结论，血小板可被组织型纤溶酶原激活剂或尿激酶激活，并且给予660mg /d乙酰水杨酸可抑制血小板激活。

项目成果

Isshiki I.Aoki N.et al: "Frequencies of prothrombin 20210G-A mutation maybe different among races." Blood Coagulation and Fibrinolysis. 9. 105-106 (1997)

Isshiki I.Aoki N.et al：“凝血酶原 20210G-A 突变的频率可能因种族而异。”

Isshiki I,Murata M,Watanabe R,Matsubara Y,Koichi K,Aoki N,Yoshino H,Watanabe G,Ishikawa K,Ikeda Y: "Frequencies of prothrombin 20210 G*A mutation may be different among races-studies on Japanese populations wiyh various forms of thrombotic disorders and h

Isshiki I、Murata M、Watanabe R、Matsubara Y、Koichi K、Aoki N、Yoshino H、Watanabe G、Ishikawa K、Ikeda Y：“凝血酶原 20210 G*A 突变的频率可能因种族而异——对日本人群的研究

Kawano K,Aoki I,Aoki N,Homori M,Maki A,Hioki Y,Hasumura Y,Terano A,Arai T,Mizuno H,Ishikawa K: "Human platelet activation by thrombolytic agents : Effects of tissue-type plasminogen activator an urokinase on platelet surface P-selectin expression" Am Hear

Kawano K，Aoki I，Aoki N，Homori M，Maki A，Hioki Y，Hasumura Y，Terano A，Arai T，Mizuno H，Ishikawa K：“溶栓剂对人血小板的活化：组织型纤溶酶原激活剂和尿激酶的作用

Matsubara Y, Aoki N.et al: "Gerotype distribution of estrogen receptor polymorphisms in men and pastmenopausal women from healthy and coronary popuktions" Arterioseler Thromb Vasc Biol. 17. 3006-3012 (1997)

Matsubara Y、Aoki N.等人：“健康人群和冠状动脉人群中男性和绝经后女性雌激素受体多态性的基因型分布”Arterioseler Thromb Vasc Biol。

Zamu T, Aoki N, et al: "A 192Arg Variant of the human parooxonase gone polymarphism is associated with an increased risk for coronary artery disease" Arterioseler Thromb Vasc Biol. 17. 3565-3569 (1997)

Zamu T、Aoki N 等人：“人类帕洛磷酶的 192Arg 变体发生多态性，与冠状动脉疾病风险增加相关”Arterioseler Thromb Vasc Biol。