Study of inhibitory effects of HMG Co A reductase inhibitor on in-vivo thrombus formation

HMG Co A还原酶抑制剂抑制体内血栓形成的研究

• 批准号: 13670768
• 负责人: KATOH Atsushi
• 金额: $ 2.3万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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/grant/KAKENHI-PROJECT-13670768/
• 关键词: Thrombus; Platelet; HMG Co A reductase inhibitor; HMGCo還元酵素阻害剤; HMG Co A 還元酵素阻害薬

To investigate whether HMG Co A reductase inhibitor inhibits in-vivo thrombus formation, we studied the effects of cerivastatin on rat carotid artery thrombus model, rat platelet activation and rat coagulation-fibrinolysis system. Cerivastatin significantly inhibited in-vivo thrombus formation. Crivastatin also significantly decreased platelet aggregation and platelet surface expression of P-selectin induced ADP, suggesting that cerivastatin inhibits platelet activation. Cerivastatin didn't affect rat plasma levels of fibrinogen, tissue factor, tissue palsminogen activating factor and tissue plasminogen activator inhibitory factor, suggesting that cerivastatin didn't affect rat coagulation-fibrinolysis system. Thus, HMG Co A reductase inhibitor may inhibit in-vivo thrombus formation by decreasing platelet activation.

为了探讨HMG-CoA还原酶抑制剂是否能抑制体内血栓的形成，我们观察了西立伐他汀对大鼠颈动脉血栓模型、大鼠血小板活化和大鼠凝血-纤溶系统的影响。西立伐他汀显著抑制体内血栓形成。克里伐他汀还显著降低P-选择素诱导的ADP诱导的血小板聚集率和血小板表面表达，提示西立伐他汀抑制血小板活化。西立伐他汀对大鼠血浆纤维蛋白原、组织因子、组织型纤溶酶原激活因子和组织型纤溶酶原激活物抑制因子水平无明显影响，提示其对大鼠凝血-纤溶系统无影响。因此，HMG Co A还原酶抑制剂可能通过减少血小板活化来抑制体内血栓的形成。

项目成果

Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T: "Mobilization of endothelial progenitor cells in patients with acute myocardial infarction"Circulation. 103. 2776-2779 (2001)

Shintani S、Murohara T、Ikeda H、Ueno T、Honma T、Katoh A、Sasaki K、Shimada T、Oike Y、Imaizumi T：“急性心肌梗塞患者内皮祖细胞的动员”循环。

Murohara T, Ikeda H, Katoh A, Takajo Y, Otsuka Y, Haramaki N, Imaizumi T: "Vitamin E inhibits lysophosphatildylcholine-induced endothelial dysfunction and platelet activation"Antioxid Redox Signal. 4. 791-798 (2002)

Murohara T、Ikeda H、Katoh A、Takajo Y、Otsuka Y、Haramaki N、Imaizumi T：“维生素 E 抑制溶血磷脂酰胆碱诱导的内皮功能障碍和血小板活化”抗氧化氧化还原信号。

Haramaki N: "Long-term smoking causes nitroglycerin resistance in platelets by depletion of intraplatelet glutathione"Arterioscler Thromb Vasc Biol.. 21. 1852-1856 (2001)

Haramaki N：“长期吸烟会消耗血小板内谷胱甘肽，导致血小板产生硝酸甘油抵抗”Arterioscler Thromb Vasc Biol.. 21. 1852-1856 (2001)

Katoh A: "Coexistence of impairment of endothelium-derived nitric oxide a nd platelet-derived nitric oxide in patients with coronary risk factors"Circ J.. 66. 837-740 (2002)

Katoh A：“患有冠状动脉危险因素的患者中内皮源性一氧化氮和血小板源性一氧化氮受损的共存”Circ J.. 66. 837-740 (2002)

Haramaki N, Ikeda H, Takajo Y, Katoh A, Kanaya S, Shintani S, Haramaki R, Murohara T, Imaizumi T: "Long-term smoking causes nitroglycerin resistance in platelets by depletion of intraplatelet glutathione"Arterioscler Thromb Vasc Biol.. 21. 1852-1856 (2001

Haramaki N、Ikeda H、Takajo Y、Katoh A、Kanaya S、Shintani S、Haramaki R、Murohara T、Imaizumi T：“长期吸烟通过消耗血小板内谷胱甘肽导致血小板中的硝酸甘油抵抗”Arterioscler Thromb Vasc Biol.. 21