Study on the treatment of highly pathogenic avian influenza H5N1 infections by means of the analysis of pathogenesis of the illness

从发病机制分析高致病性禽流感H5N1感染的治疗研究

• 批准号: 23659523
• 负责人: MORISHIMA Tsuneo
• 金额: $ 2.41万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659523/
• 关键词: インフルエンザ; 脳症; 多臓器不全; 肺炎; H5N1; 新型インフルエンザ; サイトカイン; ケモカイン; チオレドキシン; 酸化ストレス

The pathogenesis of highly pathogenic avian influenza H5N1 in humans has been closelsimilar to those of severe pneumonia and influenza-associated encephalopathy witcytokine storm. Using microarray assay we have analyzed gene expression in the acute phasof 2009pdm infection. Interestingly, gene expression profiles were different betweepneumonia patients and patients with CNS manifestations. Particularly, gene expressiorelated to ROD has been highly activated. Using mouse model, we have shown that thioredoxin-1(TRX) could suppress the oxidativstress and inflammatory changes resulting better outcome in pneumonia with influenzvirus infections. Taking together, anti-oxidant stress agents such as TRX could play an important rolin the severe pneumonia/ARD with H5N1 infections.

H5 N1亚型高致病性禽流感在人类中的发病机制与重症肺炎和流感相关脑病的细胞因子风暴非常相似。利用微阵列分析，我们分析了2009年pdm感染急性期的基因表达。有趣的是，基因表达谱在帕金森病患者和CNS表现的患者之间是不同的。特别是与ROD相关的基因表达被高度激活。在小鼠模型中，我们发现硫氧还蛋白-1（TRX）可以抑制氧化应激和炎症反应，从而改善流感病毒感染性肺炎的预后。总之，抗氧化应激药物如TRX可能在H5 N1感染的重症肺炎/ARD中发挥重要作用。

项目成果

Deaths associated with pandemic (H1N1) 2009 among children, Japan, 2009-2010.

• DOI: 10.3201/eid1711.110649
• 发表时间: 2011-11
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Okumura A;Nakagawa S;Kawashima H;Muguruma T;Saito O;Fujimoto J;Toida C;Kuga S;Imamura T;Shimizu T;Kondo N;Morishima T
• 通讯作者: Morishima T

Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated by gene expression profiling.

通过基因表达谱阐明甲型H1N1pdm09流感感染的致病机制。

• DOI: 10.1111/ped.12139
• 发表时间: 2013
• 期刊: Pediatr Int
• 影响因子: 1.4
• 作者: Yamashita N;Tsukahara H;Tsuge M;Nagaoka Y;Yashiro M;Saito Y;Fujii Y;Takashi O;Morishima T.
• 通讯作者: Morishima T.

インフルエンザ感染におけるThioredoxin binding protein 2(TBP-2)の役割

硫氧还蛋白结合蛋白 2 (TBP-2) 在流感感染中的作用

• 发表时间: 2012
• 作者: Okumura A;Nakagawa S;Kawashima H;Muguruma T;Saito O;Fujimoto J;Toida C;Kuga S;Imamura T;Shimizu T;Kondo N;Morishima T;八代 将登
• 通讯作者: 八代 将登

Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice

• DOI: 10.1097/ccm.0b013e3182676352
• 发表时间: 2013-01-01
• 期刊: CRITICAL CARE MEDICINE
• 影响因子: 8.8
• 作者: Yashiro, Masato;Tsukahara, Hirokazu;Morishima, Tsuneo
• 通讯作者: Morishima, Tsuneo

インフルエンザ感染における局所サイトカイン・ケモカインの動態

流感感染过程中局部细胞因子和趋化因子的动态变化

• 发表时间: 2012
• 作者: Okumura A;Nakagawa S;Kawashima H;Muguruma T;Saito O;Fujimoto J;Toida C;Kuga S;Imamura T;Shimizu T;Kondo N;Morishima T;八代 将登;藤井 洋輔
• 通讯作者: 藤井 洋輔