Approach for the establishment of new way of brain resuscutation

建立脑复苏新途径的途径

• 批准号: 11671524
• 负责人: MIURA Hitoshi
• 金额: $ 2.3万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671524/
• 关键词: Brain ischemia; ischemic neuronal death; mitochondrial dysfunction; calcineurin; immunosuppressant; Cyclosporin A; 神経細胞死; 脱リン酸化酵素; MRI; 三次元構築; MPT

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 as cyclosporin A (CsA) and FK506. We show here the drastic neuroprotection of the CsA in the forebrain ischemia is not only due to inhibition of calcineurininduced cell death through dephosphorylation of proapoptotic protein Bad, but also due to protection of mitochonorial damage which is caused by the MPT (Mitochondrial Permeability Transition) pore formation through cyclophilin D (CyPD), one of the prolyl cis/trans isomerase family members.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。本研究从免疫抑制剂环孢菌素A（CsA）和FK 506的作用机制方面探讨了迟发性神经元死亡的机制。我们发现，CsA对前脑缺血的神经保护作用不仅是通过抑制促凋亡蛋白Bad的去磷酸化，抑制钙调神经磷酸酶诱导的细胞死亡，而且还通过保护MPT引起的线粒体损伤通过亲环素D（CyPD）的（线粒体渗透性转变）孔形成，脯氨酰顺/反异构酶家族成员之一，这些结果为临床应用和开发治疗脑、心、肝缺血性损伤的新药提供了依据。

项目成果

Bo.K.Siesjo: "Role of mechanisms of secondary mitochondrial failure."Acta Neuroschir. 73. 7-13 (1999)

Bo.K.Siesjo：“继发性线粒体衰竭机制的作用。”Acta Neuroschir。

H.UCHIZO et al.: "A menoration by cyclosporin A of a brain damage in transient forebrain ischemen in the rat"Brain Res. 812. 216-226 (1998)

H.UCHIZO 等人：“环孢菌素 A 对大鼠短暂前脑缺血脑损伤的预测”Brain Res。

Hiroyuki Uchino^1, Futoshi Shibasaki^2, Hitoshi Miura^1, Bo.k.Siesjo^3, Atsushi Isshiki^1: "Role of calcineurin and immunophilin on ischemic brain damage and new approach for the brain resuscitation."Japanese Journal of Reanimatology. (in print). (2001)

Hiroyuki Uchino^1、Futoshi Shibasaki^2、Hitoshi Miura^1、Bo.k.Siesjo^3、Atsushi Isshiki^1：“钙调神经磷酸酶和亲免素对缺血性脑损伤的作用以及脑复苏的新方法。”日本杂志

内野博之: "虚血性神経細胞死とカルシニューソレ/イムノフイリレ情報伝達系の連関"蘇生学会誌. (掲載予定). (2001)

Hiroyuki Uchino：“缺血性神经元死亡与钙化素/免疫信息转导系统之间的关系”复苏协会杂志（2001 年）。

内野博之: "虚血性脳神経細胞死におけるカルシニューリンの分子機序-虚血性神経細胞障害に対する新規治療法確立を目指して-"医学のあゆみ. 193(12). 955-960 (2000)

Hiroyuki Uchino：“钙调磷酸酶在缺血性脑神经细胞死亡中的分子机制——旨在建立缺血性神经细胞损伤的新治疗方法——”医学史193(12)。