A nove gene therapy for Pseudomonas aeruginosa pneumonia.

一种针对铜绿假单胞菌肺炎的新型基因疗法。

• 批准号: 12671495
• 负责人: KURAHASHI Kiyoyasu
• 金额: $ 2.3万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671495/
• 关键词: cytokine; pneumonia; sepsis; Pseudomonas aeruginosa; exoenzymes; gene therapy; immune responses; macrophage

1、Preliminary experimentsThe airway instillation of isogenic mutant of Pseudomonas aeruginosa strain PA103 that is defective for production of ExoU and ExoT (PA103DUT) was shown not to cause lung injury, which was seen in the lung would be effective in preventing lung injury.2、An animal model for Pseudomonal pneumoniaWe evaluated the host response to Pseudomonas aeruginosa pneumonia and concomitant sepsis in a rat model. A manuscript is accepted for publication3、Construction of adenovirus vectorsWe have made adenovirus vector expressing the recombinant rat IL-10 gene. We also constructed adenovirus vector expressing the recombinant rat keratinocyte growth factor (KGF) gene. KGF is expected to prevent lung injury in acute lung injury for KGF is a potent growth factor for alveolar type II cells. We have confirmed the expression and production of KGF with the infection of this vector in vitro and in vivo. We are going to test the effect of the vector in an acute lung injury model.

1、初步实验铜绿假单胞菌菌株PA 103的ExoU和ExoT产生缺陷的同基因突变株（PA 103 DUT）的气道滴注被证明不会引起肺损伤，在肺中观察到的肺损伤将有效地预防肺损伤。3、腺病毒载体的构建我们制备了表达重组大鼠IL-10基因的腺病毒载体。我们还构建了表达重组大鼠角质细胞生长因子（KGF）基因的腺病毒载体。由于KGF是肺泡II型细胞的一种有效生长因子，因此有望预防急性肺损伤中的肺损伤。我们已经证实了表达和生产的KGF与感染该载体在体外和体内。我们将在急性肺损伤模型中测试载体的效果。

项目成果

K.Kurahashi, S.Ota, A.Fujita, et al.: "Beneficial effect of protective ventilation on Pseudomonas aeruginosa pneumonia."Am J Respir Critical Care Med.. 165. A788 (2002)

K.Kurahashi、S.Ota、A.Fujita 等人：“保护性通气对铜绿假单胞菌肺炎的有益作用。”Am J Respir Critical Care Med. 165. A788 (2002)

Kiyoyasu Kurahashi, Shuhei Ota, Kyota Nakamura, Yoji Nagashima, Takuya Yazawa, Minako Satoh, Asako Fujita, Ritsuko Kamiya, Eri Fujita, Yasuko Baba, Kanji Uchida, Naoto Morimura, Tomio Andoh, Yoshitsugu Yamada.: "The effect of lung-protective ventilation o

Kiyoyasu Kurahashi、Shuhei Ota、Kyota Nakamura、Yoji Nagashima、Takuy​​a Yazawa、Minako Satoh、Asako Fujita、Ritsuko Kamiya、Eri Fujita、Yasuko Baba、Kanji Uchida、Naoto Morimura、Tomio Andoh、Yoshitsugu Yamada。：“肺保护的效果

K.Kurahashi, S.Ota, A.Fujita, Y.Baba, M.Satoh, K.Nakamura, K.Uchida, Y.Nagashima, Y.Yamada.: "Beneficial effect of protective ventilation on Pseudomonas aeruginosa pneumonia."Am J Respir Critical Care Med.. 165. A788 (2002)

K.Kurahashi、S.Ota、A.Fujita、Y.Baba、M.Satoh、K.Nakamura、K.Uchida、Y.Nagashima、Y.Yamada.：“保护性通气对铜绿假单胞菌肺炎的有益作用。”Am

K.Kurahashi.: "Novel therapeutic strategy for ALI/ARDS : a consideration using animal models of acute pulmonary infection."ICU and CCU.. 27(4). 277-284 (2003)

K.Kurahashi.：“ALI/ARDS 的新治疗策略：使用急性肺部感染动物模型的考虑。”ICU 和 CCU.. 27(4)。

倉橋 清泰: "急性肺感染症モデルを用いた肺傷害の治療法"ICUとCCU. 27. 277-284 (2003)

Kiyoyasu Kurahashi：“使用急性肺部感染模型治疗肺损伤”ICU 和 CCU。 27. 277-284 (2003)