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.

人类高致病性禽流感H5N1的发病机制与重症肺炎和流感相关脑病脑病风暴非常相似。使用微阵列分析，我们分析了 2009pdm 感染急性期的基因表达。有趣的是，肺炎患者和有中枢神经系统表现的患者之间的基因表达谱不同。特别是与ROD相关的基因表达被高度激活。使用小鼠模型，我们发现硫氧还蛋白-1 (TRX) 可以抑制氧化应激和炎症变化，从而在流感病毒感染性肺炎中​​获得更好的治疗效果。总而言之，TRX 等抗氧化应激剂可能在 H5N1 感染引起的严重肺炎/ARD 中发挥重要作用。

项目成果

Unexpected cardiopulmonary arrest associated with influenza: our experience during the 2009 pandemic in Japan.

• DOI: 10.1111/irv.12032
• 发表时间: 2013-09
• 期刊: Influenza and other respiratory viruses
• 影响因子: 4.4
• 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

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

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

Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy

脑损伤生物标志物对急性脑炎/脑病的预后价值

• DOI: 10.1111/ped.12094
• 发表时间: 2013
• 期刊: Pediatr Int.
• 作者: Tsukahara H;Fujii Y;Matsubara K;Yamada M;Nagaoka Y;Saito Y;Yashiro M;Tsuge M;Goto S;Kitamura T;Hata A;Ichiyama T;Morishima T
• 通讯作者: Morishima T