Pharmacological investigation for mechanisms of cerebral hemorrhage induced by anti-thrombotic agents

抗血栓药物致脑出血机制的药理学研究

• 批准号: 15390173
• 负责人: UMEMURA Kazuo
• 金额: $ 6.34万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390173/
• 关键词: stroke; cerebral hemorrhage; heparin; tPA; MMP-9

Cerebral hemorrhage associated with antithrombotic and thrombolytic therapy in acute stroke is a major clinical problem. We investigated the roles of endogenous tPA and MMPs in hemorrhagic cerebral infarction associated with heparin. We demonstrated that heparin administration caused cerebral hemorrhage in WT but not in KO. Heparin administration increased tPA activity and its mRNA expression in WT. We also observed an induction of MMP9 and its mRNA expression by heparin administration in WT but not in KO. Our findings suggest that endogenous tPA plays an important role in heparin-produced cerebral hemorrhage via MMP9 induction and activation.

脑出血与抗栓和溶栓治疗急性脑卒中是一个主要的临床问题。我们研究了内源性tPA和MMPs在肝素相关出血性脑梗死中的作用。我们证明了肝素给药引起WT脑出血，但在KO中没有。肝素给药增加WT中tPA活性及其mRNA表达。我们还观察到了诱导MMP 9及其mRNA表达肝素管理WT，但在KO。我们的研究结果表明，内源性tPA通过MMP 9诱导和激活在肝素引起的脑出血中起着重要作用。

项目成果

Neuroprotective effects of ONO-1924H, an inhibitor of poly ADP-ribose polymerase (PARP), on cytotoxicity of PC12 cell s and ischemic cerebral damage.

聚 ADP 核糖聚合酶 (PARP) 抑制剂 ONO-1924H 对 PC12 细胞的细胞毒性和缺血性脑损伤的神经保护作用。

• 发表时间: 2004
• 期刊: Life Sciences 76
• 作者: Kamanaka;Y.;Kondo;K.;Suzuki;Y.;Nakamura;Y.;Umemura;K.
• 通讯作者: K.