Elucidation of the molecular mechanisms of influenza-associated encephalopathy due to disorder of ATP generation in mitochondria

阐明线粒体 ATP 生成障碍导致流感相关脑病的分子机制

• 批准号: 21790992
• 负责人: CHIDA Junji
• 金额: $ 2.75万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790992/
• 关键词: インフルエンザ脳症(IAE); 多臓器不全(MOF); ミトコンドリア; 脂肪酸代謝不全; アデノシン三リン酸(ATP); インフルエンザ; 脳症; 脂肪酸代謝; サイトカイン; 分子生物学; MOF(多臓器不全); 脂肪酸代謝障害; ATP(アデノシン三リン酸)

Severe influenza including influenza-associated encephalopathy (IAE) is characterized by cytokine storm and multi-organ failure (MOF) with severe edema. However, the relationship amongst factors, such as cytokine storm, hyper-vascular permeability, and metabolic disorders, remain unclear. We generated gene targeted mouse models of the CPT2 variants, analyzed ATP levels in various organs of severe influenza, and found significant ATP depletion after virus infection. We conclude that ATP depletion in various organs elicited sudden-onset of brain edema and MOF in associated with influenza virus-cytokine-protease cycle. To address this problem, we have established a clinically applicable drugs and diagnostic assessment strategy.

包括流感相关脑病（IAE）在内的严重流感的特征是细胞因子风暴和伴有严重水肿的多器官衰竭（MOF）。然而，诸如细胞因子风暴、高血管通透性和代谢紊乱等因素之间的关系仍不清楚。我们产生了CPT 2变异体的基因靶向小鼠模型，分析了严重流感的各种器官中的ATP水平，并发现病毒感染后ATP显著耗竭。我们的结论是，在各种器官的ATP耗竭引起突发性脑水肿和MOF与流感病毒-细胞因子-蛋白酶循环。为了解决这个问题，我们已经建立了一个临床适用的药物和诊断评估策略。

项目成果

Boost of mucosal secretory IgA response by clarithromycin (CAM) in paediatric influenza.

克拉霉素 (CAM) 在小儿流感中增强粘膜分泌型 IgA 反应。

• 发表时间: 2009
• 期刊: Respirology 14(8)
• 作者: Sawabuchi T;et al.(他8名;8番目)
• 通讯作者: 8番目)

Influenza-cytokine-protease cycle in the pathogenesis of vascular hyper-permeability in severe influenza and its possible treatment

流感-细胞因子-蛋白酶循环在重症流感血管通透性过高发病机制中的作用及其可能的治疗

• 发表时间: 2010
• 作者: 木戸博;他
• 通讯作者: 他

Influenza Virus-Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza

• DOI: 10.1086/656044
• 发表时间: 2010-10-01
• 期刊: JOURNAL OF INFECTIOUS DISEASES
• 影响因子: 6.4
• 作者: Wang, Siye;Le, Trong Quang;Kido, Hiroshi
• 通讯作者: Kido, Hiroshi

Mechanisms of matrix metalloprotease-9 up-regulation and tissue destruction in various organs in influenza A virus infection.

甲型流感病毒感染中各器官基质金属蛋白酶9上调和组织破坏的机制。

• 发表时间: 2010
• 期刊: The Journal of Medical Investigation 57(1-2)
• 作者: Wang S;et al.(他6名;3番目)
• 通讯作者: 3番目)

Mechanisms of matrix metalloprotease-9 up-regulation and tissue in various organs in influenza A virus infection

甲型流感病毒感染中基质金属蛋白酶9上调及各器官组织机制

• 发表时间: 2010
• 期刊: The Journal of Medical Investigation 57(1-2)
• 作者: 小林弘典;虫本雄一;山口清次;Kazuyuki Ikeda;木戸博;小林弘典;Kazuyuki Ikeda;Wang S
• 通讯作者: Wang S