New approach to investigate the mechanisms of Ischemic neuronal death and development for the establishment of new way of brain resuscutator

探讨缺血性神经元死亡和发育机制的新途径，建立脑复苏新途径

• 批准号: 14571467
• 负责人: UCHINO Hiroyuki
• 金额: $ 2.24万
• 依托单位: Tokyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571467/
• 关键词: Calcineurin; Cyclophillin D; CsA; CsJ; NCX; MPT; Brain ischemia; DNA chip; Knock out mouse; 脳虚血; 神経細胞死; Cyclophilin D; Calcineurin; MPT; CSJ; Ca2+ exchanger; 脳保護

Brain ischemia leads to severe damage in the form of delayed neuronal cell death. We have been investigated the mechanisms of delayed neuronal cell death in terms of the mechanisms of immunosuppressant, such a cyclosporin A(CsA) and FK506. From our results, Calcineurin and immunophilin signal transduction casca* play an important roles for neuroprotection, Especially, mitochondrial isomerase cyclophillinD paly a pivotal role to regulate the MPT(Mitochondrial Permeability Transition)pore formation, one of the prolylcis/trans isomerase family members.We also need further analysis to explore more mechanisms.These results shed light on the clinical application and development of new drugs for the treatment of ischemic damage in the brain as well as in the heart and liver.

脑缺血导致严重的损伤，表现为迟发性神经元细胞死亡。我们从免疫抑制剂环孢菌素A（CsA）和FK 506的作用机制方面研究了迟发性神经元细胞死亡的机制。结果表明，钙调神经磷酸酶和亲免素信号转导通路casca* 在神经保护中起重要作用，尤其是线粒体异构酶cyclophillin D在调节MPT中起关键作用（线粒体渗透性转换）孔形成，其中一个脯氨酰顺式/本研究结果为临床应用和开发治疗糖尿病的新药提供了依据，大脑以及心脏和肝脏的缺血性损伤。

项目成果

Shibasaki F, Ulrika Hallin, Hiroyuki Uchino: "Calcineurin as a multifunctional regulator"J. Biochem. 131. 1-15 (2002)

Shibasaki F、Ulrika Hallin、Hiroyuki Uchino：“钙调神经磷酸酶作为多功能调节剂”J。

Shibasaki F, Hallin U, Uchino H.: "Calcineurin as a multifunctional regulator"J Biochem(Tokyo). 131(1). 1-15 (2002)

Shibasaki F、Hallin U、Uchino H.：“钙调神经磷酸酶作为多功能调节剂”J Biochem（东京）。

内野博之, 芝崎 太, Bo.K.Siesjo, 一色 淳: "虚血性神経細胞死とカルシニューリン/イムノフィリン系の役割と新規脳蘇生法確立への応用"蘇生. 21. 1-8 (2002)

Hiroyuki Uchino、Futoshi Shibasaki、Bo.K.Siesjo、Jun Isshiki：“缺血性神经元死亡和钙调神经磷酸酶/免疫亲和素系统的作用及其在建立新的脑复苏方法中的应用”复苏。 ）

Shibasaki F, Hallin U, Uchino H.: "Calcineurin as a multifunctional regulator."J Biochem (Tokyo). 131(1). 1-15 (2002)

Shibasaki F、Hallin U、Uchino H.：“钙调神经磷酸酶作为多功能调节剂。”J Biochem（东京）。

H.Uchino, BK Siesjo, F.Shibasaki: "Calcineurin and immunophilin are pivotal target for delayed neuronal cell death on the forebrain ischemia in the rat."Acta Neurochirurgica Supplement Springer Verlag Wien New York. (in press). (2003)

H.Uchino、BK Siesjo、F.Shibasaki：“钙调磷酸酶和亲免素是大鼠前脑缺血延迟性神经元细胞死亡的关键靶标。” Acta Neurochirurgica Supplement Springer Verlag Wien New York。